Personal Courage Essay Example | Topics and Well Written Essays - 250 words

Individual Courage - Essay Example I have depicted individual boldness in two perilous and dangerous situations to spare an actual existence. The primary occurrence or situation was in a consuming house. It was a neighbor’s a house and everyone had left with the exception of a small kid who was left resting inside. The inferno had overpowered the structure and regardless of the danger of hurting myself, I chose to take fearlessness to spare the little blameless youngster. It was testing and in spite of the smoke and warmth I figured out how to spare the little youngster. In this way, it is because of individual fearlessness that empowered me to prevail in the salvage. The subsequent occurrence or situation was to spare my companion who had been assaulted. He was grabbed by raucous folks nearby and being tormented. I realized my companion was not off-base subsequently it was unscrupulous for them to exercise such a brutal follow up on him. Along these lines, I moved toward them in mental fortitude and assaulted the posse head. I won the battle, and my companion was at long last free. Accordingly, individual mental fortitude is a noteworthy goodness that is suggested for one’s security and

Piaget’s Theory Of Child Development Samples †MyAssignmenthelp.com

Question: Talk about the Piagets Theory Of Child Development. Answer: Asset plan: Ball made out of paper for babies In youth instruction setting, paper make exercises like creation ball out of papers can assist with upgrading innovativeness of kids and advance visual learning. By taking part in such sort of paper works, little children can build up their engines abilities, basic reasoning aptitudes and innovativeness (Cremin et al., 2015). This sort of play experience identifies with the Piagets hypothesis of youngster advancement, which expresses that kids build up their speculation abilities by association with world outside (Demetriou, Shayer Efklides, 2016). Subsequently, when a baby takes part in exercises like structure ball out of papers, they get an encounter that advances the sensible and calculated development of kids. Setting: Various shades of workmanship papers will be put in action room with the goal that youngsters have enough space to find out about creation balls Two major tables with five to six seats will be masterminded in the room so kids can sit serenely and keep all the materials expected to set up the balls Six babies will be associated with the action under the management of a kid care teacher A few boxes will be kept with the goal that kids separate the balls as indicated by hues Learning result: Taking part in craftwork of making paper balls will push the little child to: Build up their engine abilities by utilizing the scissors for slicing and utilizing the papers to jot with pastels and make designs Fortify their critical thinking and basic intuition abilities by the experience of taking choices in regards to how to orchestrate the paper to make balls Find out about shading, shape and utilizing expressive words to disintegrate papers. This is significant for language improvement of little children Advance social improvement of kids by allowing them the chance to work with other kids to make the balls Improve their innovative and consider better approaches to utilize the paper (pbs.org, 2018). Movement: Every youngster will be approached to collaborate with other kid to set up the balls Initially, the instructor will exhibit the best approach to make the ball out of specialty papers and afterward every youngster will be solicited to make their balls out from create papers gave Every kid will be offer a few unique shades of specialty paper and requested to keep the balls in coordinating shading boxes While utilizing the art paper, instructor will show babies various shapes and hues Kids will likewise be approached to show their imagination by making various examples on the paper balls. Specialty papers are brilliant assets that draw in the consideration of little children and increment their enthusiasm for finding out about the new action of making papers from a bit of paper. This sort of learning experience doesn't require a lot of asset and youngsters get the opportunity to upgrade their dynamic and innovative reasoning abilities as well. By permitting them to work two by two, they additionally get the chance to learn social abilities and coordination aptitudes, which is likewise a significant territory of youngster learning and improvement (Huang et al., 2014). References: Cremin, T., Glauert, E., Craft, A., Compton, A., Stylianidou, F. (2015). Inventive Little Scientists: investigating instructive cooperative energies between request based and innovative methodologies in Early Years science.Education 3-13,43(4), 404-419. Demetriou, A., Shayer, M., Efklides, A. (Eds.). (2016).Neo-Piagetian hypotheses of intellectual turn of events: Implications and applications for training. Routledge. Huang, J., Sherraden, M., Kim, Y., Clancy, M. (2014). Impacts of Child Development Accounts on early social-enthusiastic turn of events: An exploratory test.JAMA pediatrics,168(3), 265-271. pbs.org (2018). The Importance of Art in Child Development. Recovered 2 March 2018, from https://www.pbs.org/guardians/training/music-expressions/the-significance of-craftsmanship in-kid advancement/

Blog Archive From Finance to Food ChowNow Co-Founder Chris Webb Shares His Entrepreneurial Story

Blog Archive From Finance to Food ChowNow Co-Founder Chris Webb Shares His Entrepreneurial Story Chris Webb, Co-Founder of ChowNow Today, many aspiring MBAs and MBA graduates want to join start-ups or launch such companies themselves. Is entrepreneurship as exciting as it seems? Is it really for you? mbaMission Founder Jeremy Shinewald has teamed up with Venture for America and CBS Interactive  to launch  Smart People Should Build Things: The Venture for America Podcast. Each week, Shinewald interviews another entrepreneur so you can hear the gritty stories of their ups and downs on the road to success. Chris Webb began his career when he was only 19 by accepting a full-time position at former investment bank Bear Stearns. Following a decade-long career in finance, a surprising source introduced Webb to the food business, andâ€"after making a few detoursâ€"he co-founded online ordering system ChowNow in 2010. Tune in to the podcast to hear about Webb’s progress throughout the years as he discusses these details and more: Why a gap in the food market caught Webb’s interest despite his background in a completely different field How he and co-founder Eric Jaffe created a fictional prototype of what eventually became ChowNow to test the client waters… …and how many restaurateurs were instantly interested (hint: dozens!) This entrepreneurial story is only one of more than 40 available in our podcast series. Subscribe today to catch them all! Share ThisTweet News

Deaf Like Me by Thomas S. Spradley and James P. Spradley

Have you ever felt like there was nothing that you can do for your child? In this book, Deaf Like Me, by Thomas S. Spradley and James P. Spradley, I can see the journey that Lynn’s parents took to get her help. (Spradley Spradley, 1978). This book was an excellent read. I really liked the way that they described the ways they tried to help Lynn to understand the world around her. The book, is a great asset for any family that might be unexpectedly put into a situation that they know nothing about such as a deaf child. The author Thomas S. Spadley is Lynn’s father. He is the one that was with them all the time and saw all that his wife Louise tried for their daughter to understand them. The greatest qualification for him to write†¦show more content†¦Overall, his perspective helped to make the book a little more interesting in that he was not all the time there. Lynn’s deafness was found through a series of many events. These events consisted of seein g many doctors to see if she could hear or not. Lynn was taken to a doctor to make sure that her ears where fully developed, this doctor said that she was fine. Lynn was also taken to a speech therapist that told them that she could learn and that all she needed was to be talked too. Just talking to her would do it all and that one day she would be able to talk to them. This information gave them some hope that she would be able to communicate someday. They also tried the John Tracy course to help her better learn to lip read to be able to talk to them. This had over a thousand classes to it and things for the family to do. Which they tried intensely with Lynn and did the games and things that came with it with her on a daily basis. (79). Some of the reasons that they thought Lynn could hear where: that when she was six months old, Lynn, had started to make noises and babble (27).No baby could do that except if they hear the noises around them. Then when she was about two she was taken to get a hearing test done. The Audiologist told them,† That she could hear at 90 decimals at her hearing test†. The Audiologist did not say that she was completely deaf, so there was hope (45). This is when they started other things to help Lynn. They got in touch with people aroundShow MoreRelatedDeaf Like Me by Thomas S. Spradley and James P. Spradley1606 Words   |  7 Pages Have you ever felt like there was nothing that you can do for your child? In the book, Deaf Like Me, by Thomas S. Spradley and James P. Spradley, I can the journey that Lynn’s parents had to take to get her help. This book was excellent I really liked the way that they described the ways that they tried to help Lynn to understand the world around her. In this book, I also saw how a mother and father will do anything for their child so that they can understand all that is around them. This book,Read MoreEssay on Deaf Like Me1324 Words   |  6 PagesClayton 4/15/ 2010 ASL Research Paper Deaf Like Me By Thomas S. Spradley James P. Spradly Epilogue By Lynn Spradley Deaf Like Me is a story compiled together by Thomas and James Spradley. It is a compelling story about two hearing+ parents struggling to cope with their daughters overwhelming deafness. This powerful story expresses with simplicity the love, hope, and anxieties of all hearing parents of deaf children. In the epilogue, Lynn Spradley, herself, now a teenager thinks back about Deaf Like Me by Thomas S. Spradley and James P. Spradley Have you ever felt like there was nothing that you can do for your child? In the book, Deaf Like Me, by Thomas S. Spradley and James P. Spradley, I can the journey that Lynn’s parents had to take to get her help. This book was excellent I really liked the way that they described the ways that they tried to help Lynn to understand the world around her. In this book, I also saw how a mother and father will do anything for their child so that they can understand all that is around them. This book, is also a great asset to any family that might be unexpectedly thrown into a situation that they do not expect such as a deaf child. The author Thomas S. Spadley is Lynn’s father. He is the one that was with them all the time and saw all that his†¦show more content†¦In this school they wanted for all the children to be oral by the time that they got to kindergarten and be ready for regular academics. (148) this was there second time with professionals that had their ide as of what a deaf child should be able to do. Lynn started school with a teacher named Ms. Taylor that began to teach the children so that they could recognize what they needed to be successful later on in their schooling. Dr. Barrington, a psychologist, taught a class to the parents of deaf children on how to read to them so that they understand. (175) this is where the Spradleys’ learned that the more they read to Lynn the better she would understand them and be able to lip read what they were saying. Lynn also went to the Starr school that they wanted to keep as an Oral school, so she had to learn to speak. (207) When going to a PTA Meeting for the school, this is when Louise and Tom saw a deaf couple signing to each other. This is when they met with Bill and Kim that taught them that Lynn could learn to sign and that it would be a good thing for them to learn also. In the first week Lynn could sign thirteen words that she had already knew and just did not have anything to go along with the word. As the family learned more and more about Lynn and her deafness, the reader can see that they began to accept it. The changes all came slowly, the more that they learned about the disability that Lynn had. The reader can see that at first they did notShow MoreRelatedDeaf Like Me by Thomas S. Spradley and James P. Spradley1665 Words   |  7 PagesHave you ever felt like there was nothing that you can do for your child? In this book, Deaf Like Me, by Thomas S. Spradley and James P. Spradley, I can see the journey that Lynn’s parents took to get her help. (Spradley Spradley, 1978). This book was an excellent read. I really liked the way that they described the ways they tried to help Lynn to understand the world around her. The book, is a great asset for any family that might be unexpectedly put into a situation that they know nothingRead MoreEssay on Deaf Like Me1324 Words   |  6 PagesClayton 4/15/ 2010 ASL Research Paper Deaf Like Me By Thomas S. Spradley James P. Spradly Epilogue By Lynn Spradley Deaf Like Me is a story compiled together by Thomas and James Spradley. It is a compelling story about two hearing+ parents struggling to cope with their daughters overwhelming deafness. This powerful story expresses with simplicity the love, hope, and anxieties of all hearing parents of deaf children. In the epilogue, Lynn Spradley, herself, now a teenager thinks back about

Indonesia in the 1980s - 1213 Words

Indonesia’s industrialisation policies play an important role in supporting the achievement of high and sustained economic growth. The move towards export promotion from import substitution in the mid-1980s succeeded in restructuring the economy from agriculture to semi-industrious. As a result, the role of industry within the economy has become increasingly important, and whilst it has been successful within its own sphere of socio-economic prosperity and sustainability, in relative terms, Indonesia has still been outperformed by the 4 ASIAN tigers. Whilst bold and decisive redirection of economic policy is effective, if the implementation and execution of new policies fails to anticipate the demands of a competitive international market, then those policies will be of significantly less worth in a global context. The fiscal policies of the island group just north of Australia need to be flexible to allow for a changing, growing market, the pro-active approach. Indonesia is the largest economy in South East Asia, primary industry of industry (47%), agriculture (15%) and a service industry that makes up nearly 40% of the GDP. More than 1,000 islands totalling almost 2,000,000sq/km make up the largest archipelago in the world. In 2012 the labour force stood at 120 million, 16 times the population of NSW. So what we have is a top 20 economy with a huge workforce and natural resources worth 10s of billions a year. Stepping back to a pre-Suharto Indonesia (for its contextualShow MoreRelated Indonesian Demographic Transition Essay1563 Words   |  7 Pagesthis paper intends to explain why the change of population structure has an effect on the society’s economic condition in Indonesia with examining the demographic variables. This short paper is aimed to support the hypothesis that the demographic variables are important influential factors on the economic development and significantly affect on the social welfare in Indonesia. Therefore, the paper proceed with examining the demographic transition from 1970 to 2000 in the change of population structureRead MoreThe Struggle For Freedom And Freedom1277 Words   |  6 PagesPhilippines and Indonesia, both faced the same post colonization events in the sense that regained their independence from colonial powers, faced dictatorship, and ultimately won their freedom with the exception that they took a little different path in achieving this path. Japan was the driving force in the invasion and finally the independence of Indonesia and Philippines. In 1945 Japan invaded the East Indies. Until 1942 Indonesia was under the ruling of Netherlands. Indonesia under the Netherlands’sRead MoreAustralia s Relationship With Indonesia1712 Words   |  7 Pagesthe foreign relations between the two countries, whether economically, politically, legally or socially. Australian-Indonesian relations involve an interaction in foreign policies between the two nations (Wolfsohn, 1951, p. 68). As long as Indonesia is Australia s closest and largest neighbor, they are bound to have great international relations. These relations began as early as the 17th century and had only become enhanced with time (Daly, 2003, p. 397). The relationship has been defined by a conjointRead MoreFilm Industry in CIVET Countries1271 Words   |  5 Pagesengaged in (Stock, 1997, pg 60). Indonesia The film industry in Indonesia has been gathering momentum after a decline that started in the 1980s. In December 2005, she held her second Indonesia Film Festival (IFF) after a barren 12 years in the film industry. In this event, 27 films were nominated for the various categories available. Riri Rezas movie Gie scooped the prestigious best film award in the event. The decline in the film industry observed after the 1980s was mainly due to the emergenceRead MoreMalaysia s Income Inequality Trend Essay863 Words   |  4 Pagesmost volatile GDP per capita and GDP per capita growth rate whereas Indonesia has most stable GDP per capita and GDP per capita growth rate which are unaffected by global economic recession and other global economic factors. Figure 5. GDP per capita from 2007 to 2015 Figure 6. GDP per capita growth rate from 2007 to 2015 4. Income Inequality Figure 7. Income inequality trend From the figure 7, we can infer that Indonesia has lowest Income inequality, but in the recent few years, the seemsRead MoreLenzing Ag Case1197 Words   |  5 PagesLenzing AG: Expanding in Indonesia Case Review Summary Lenzing AG is one of the worlds largest rayon fiber manufacturers, originating in Lenzing, Austria.   In 1938 Lenzing AG was founded, starting pulp and viscose fiber production. Up until the 1980’s, Lenzing was a company that held its production and management in the same country and town where the company had originated. Until one day , the Chairman of Lenzing had agreed to go into a joint partnership with an international investorRead MoreA Brief History Of Country Since 19492324 Words   |  10 PagesReport - Indonesia A brief history of that country since 1949: Indonesia was acknowledged to be an independent country from Netherlands in 1949, and has experienced sharp downturns as well as booms within their business cycle. In the 1960 s Indonesia s economy rapidly declined due to political instability, the government was too inexperienced to understand and maintain a stable economy, thus resulting in a major economic recession where inflation was at 1000% , there was minimal foreign investmentRead MoreCompany Analysis : Khs Gmbh1734 Words   |  7 Pagescould sort out the problem according to the management. Indonesia is an option that the company management is looking forward to start the production. The strategic location in relation to giant economies of China, India and Australia, low labour cost and access via sea route are the main advantages that Indonesia has. But, being a complex country, there are certain risks that the company should keep an eye on before investing in Indonesia. 1.INDONESIAN ECONOMY IndonesianRead MoreOpec And The Price Of Oil873 Words   |  4 Pagesorganization were Iran, Iraq, Kuwait, Saudi Arabia and Venezuela. These five states were later joined by nine other countries: Qatar (1961), Indonesia (1962), Libya (1962), United Arab Emirates (1967), Algeria (1969), Nigeria (1971), Ecuador (1973), Gabon (1975), and Angola (2007). Ecuador and Gabon withdrew from the organization in 1992 and 1994 as Indonesia in 2007 respectively. OPEC relocated its headquarters from Geneva to Vienna in 1960. The purpose of OPEC, as with any cartel, is to limit suppliesRead MorePalm Oil Is The World s Most Common Oil1021 Words   |  5 Pagesvegetable oil. The global demand for this commodity has increased over the years creating expansions of plantations in Indonesia leading to biodiversity loss, forest fires, peat degradation, hardship on families and a range of social issues. Since the early 1980’s palm oil has more than tripled globally primarily in Indonesia. â€Å"Most of this expansion has occurred in Indonesia, where the total land area of oil palm plantations increased by over 2100 per cent (more than 22 times greater) over the

Computer and Globalization - 786 Words

A computer Technology has been a great deal of discussion in recent years about globalization, which can be defined as â€Å"the intensification of economic, political, social and cultural relations across borders.† Evidence of globalization is seen in our daily lives. We are being influenced by the on rush of economic and ecological forces that demand integration and uniformity and that mesmerize the world with fast music, fast computers and fast food with MTV, Macintosh and McDonald’s, The impact of internet on globalization has both positive and negative aspects. The positive impact of the internet technology on globalization include the modernization and improvement in the business sector on a world wide basis. Businesses improve their†¦show more content†¦An aspect of the world which has gone through the process can be said to be globalized. Direct acquisitions wrest financial control, profits, and editorial decision-making and jobs from nationals, paving the way for further exploitation of already existing editorial investment made by the parent company. Cases: (1) In Hungary, before his death Maxwell acquired a colour printing plant and interests in the leading morning paper of Budapest Magyar Hirlap, and an evening paper, Esti Hirlap. After taking over the former paper he fired 30 journalists. (2) Also in Hungary, Murdoch purchased 50% control of two newspapers, Mai Nap and Reform, the latter with an estimated circulation of 430,000 and an estimated readership of 1.5 million. Sample front pages resembled Murdochs other scandal sheets. Mai Nap also announced plans to acquire the countrys first national commercial private TV channel (Advertising Age, May 14, 1990, p. 37f.). (3) The Axel Springer group bought seven of Hungarys 19 provincial dailies (World Press Freedom Committee, 1990, p. 5). Advertising serves two roles. It transforms the operation of an information vehicle fundamentally. The enterprise becomes a vehicle for the sale of its audience to advertisers. Secondly, advertising provides advantages toShow MoreRelatedCulture Globalization and Its Impact on Recreation Culture1353 Words   |  6 Pagestwenty century until that day by globalization theory, its concept and future impacts . the scientists opinions had varied about globalization repercussions at rising countries including the Arab and Islamic countries . cultural globalization is one of globalization fields which correlated by cultural side , all life fields impacted by globalization , the sport field is one of fields which impact by social phenomenon what appear on societies , but globalization appearance and its effect on anyRead MoreGlobalization, No Alliances, And No Communication?1267 Words   |  6 Pagesthrough a process of globalization that makes possible to say that the answer for this que stion is a strong no. According to Hirst, Thompson, and Bromley â€Å"It is widely asserted that we live in an era in which the greater part of social life is determined by global processes, in which national cultures, national economies, national borders and national territories are dissolving. Central to this perception is the notion of a rapid and recent process of economic globalization† (2015). Nowadays it isRead MoreMajor Forces That Are Leading International Firms Essay743 Words   |  3 PagesThere are five major forces that are leading international firms to the globalization of their operations which includes (1) political (2) technological (3) market (4) cost and (5) competition. Many firms initiate international operations to gain assess by combined markets through exporting product or producing within the area. Technological According to (Ball, 2011) today’s technology has allowed an advance in computers, communication and an increase flow of ideas. Through the internet and networksRead MoreThe Impact of Technology on Business Essay1069 Words   |  5 PagesThe computer has introduced the world to the internet. The internet has brought us into a new age of development. Through computer technology and internet development, business are rapidly developing and at the same speed changing. The introduction of computers has given business an interesting upper hand by supplying companies with endlessly amounts of information. The Computer age, also known as, the Information age developed an environment of free flowing information. Between theRead MoreAssess the view that the process of globalization has led to changes in both the amount of crime and the types of crime committed1207 Words   |  5 Pagesï » ¿Assess the view that the process of globalization has led to changes in both the amount of crime and the types of crime committed. The globalization of crime has become a renowned problem for the law worldwide; as societies become more interconnected, an act in one country can have repercussions in another which is across another continent. This is primarily down to technological developments, as nowadays communication between countries is simple compared to decades ago. Alongside this transportRead MoreEssay on Computer Science: Key for Modern Day Innovation985 Words   |  4 PagesAges, that is, zero. However, there is a large border between innovation in the past and innovation today. This is because major branches of technology have already been discovered. One example of a major branch of technology is ICT. Consequently, Computer Science and the Internet could revolutionize the modern world and make tasks, known as difficult beforehand, simpler and could potentially increase innovation rate tenfold. Innovation growth may be plummeting down, although, Smart (2005) believesRead MoreThe Proliferation of Technology in Developing Countries1319 Words   |  6 PagesDefine globalization 1.0, 2.0, and 3.0 and provide a sample of the type of business data managers collected during each era. Thomas Friedman contends that globalization 1.0 shrunk the world from large to medium and countries and governments were the main protagonists. The governments of countries would finance explorers like Christopher Columbus to discover new parts of the world to enhance trade and commerce. The governments financed the explorers through the exports of manufactured goods and byRead MoreApplication Of The New Digital Technologies Into All Aspect Of Business851 Words   |  4 PagesThe act of collaboration and incorporation among governments, people and companies in the different part of the globe in called globalization. The rising or the integration of globalization has had impact in the various aspect of mankind. Information technology has aided in the various aspect of globalization which include international trade and investment, education, health, environment, media, culture, human right and among others. The effects on these aspects of the well-being of the societyRead MoreThe Ben efits Of Globalization1525 Words   |  7 Pagesâ€Å"It has been said that arguing against globalization is like arguing against the laws of gravity† (Kofi Annan, Former Secretary General of the United Nations). Globalization has had and will continue to have a lasting impact on our modern every-day lives. While some United States citizens may not even be able to locate Beijing, China on a map, they sure do purchase many goods that were made there. Globalization is a concept with many meanings and interpretations that have made many people very confusedRead MoreCase Study: Vizio1305 Words   |  6 PagesTVs. However, most importantly Vizio’s unique use of globalization of production which gave them a competitive advantage in the market just as it was peaking. I found it important to do some research on the Vizio company to get a solid understanding of their background and history. The unique blend of origin, ethnicity and country of residence through much of his youth may have played a strong role in CEO, William Wang’s success with globalization. What started as a consultant business in 2002, later

Comparing For Profit and Non for Profit Colleges free essay sample

Colleges and university have slowly become one of the stepping stones into the working world today. People go to colleges for higher education with the intention of earning degrees in which they can use in their respective fields. Some example degrees that people pursue are Medical, Law, Business, Accounting, and Science Degrees. Through the years the idea of college was that it was optional and it was a door for better life and job. However in the modern times, it become a necessity. It all started when the colleges once single- gender institutions target specific students in their respective demographics. Today, the college market has now been divided into two major categories: Not-for-Profit Colleges and For-Profit colleges. Not-For-Profit Colleges are institutions that are interested in serving the students needs by providing necessary education to the student. The Not-For-Profit organization are tax exempt and have a board of trustees that makes decisions. For-Profit Colleges are run like a business in which their goal is to generate income for their owners and shareholders. There are no board of trustees at For-Profit College and the owner and shareholders control the decision on which is best for the institution. Although the objective for both Not-for-Profit Colleges and For-Profit College is to provide their students an education in which they can use for their future, both institution have great differences in which their organizations are run. Although the primary objective For-Profit colleges is to provide an education, they are merely a business in which their goal is to earn a profit. Like any business, the For-Profit Colleges can be setup as a sole proprietorship, partnership, or even a subsidiary of a larger company. The For-Profit College can also be setup as a corporation that have stocks traded on the stock markets. They will try to bring earnings and a return on investment for all their shareholders and investors. They can have great flexibility because at the end of the day, the goal for the For-Profit College is to make money and only that. The instructors that are hired at For-Profit Colleges usually have a very different approach to their teaching compared to Non-For-Profit Colleges. Usually they are merely there to carry out the lesson plans in which was designed by the institution. Majority of the lesson plan given to each student is standard which means the instructors do not have the liberty to create their own curriculum or lesson plans. This is also due to the purpose of the education given is to assist the student in getting specific jobs with specific job functions. The courses at the For-Profit college is to help the students get better jobs in the market while the courses at Not-For-Profit College intend to allow the student learn and grow within their respective fields. Students that enter For-Profit colleges already have a plan in terms of type of jobs they would like to pursue and they enroll in the necessary courses while some students at Not-For-Profit College have no idea which career that they would like to pursue. Not-For-Profit college help you learn and gain the knowledge in the field that youre interested in while For-Profit colleges prepare you for the specific job that you want to do. The admission process for For-Profit schools are not as selective as the one in Not-For-Profit College. There isnt much prior evaluation of the student since their main goal is to make a profit. They tend to be more flexible in terms of their requirements and appeal to students of all ages and races. Modern day classes can be taken online and at more convenient times such as nights and weekends to accommodate students that work full time. Online has also been the new trend because of the lower overhead costs for the For-Profit institution. For-Profit institutions tend to not have a campus like the Not-For-Profit colleges do. For-Profit colleges classes is usually at their own building or leased space. There isnt any services such as on-campus food or housing that is available to the students at For-Profit institutions. The college provides students with the education that they need for their desire jobs rather than a college experience that a Not-For-Profit college can provide. For Profit institutions conduct their accounting the same as any regular business would do. Their main goal is to make a profit just like all businesses would do. For-Profit institutions must comply with the Federal Accounting Standard Board. The tuitions are recorded as revenue while the expenses include leases, staff, and maintenance expenses. For-Profit colleges budget system must include tools to forecast budgets, manage variance and generate financial reports. The budget forecast is designed to estimate revenue and expenses to its income center, administrative cost structure, and its academic schedule. The income center budget includes enrollments, revenue, and expenses by academic period. Administrative expenses include administrative costs per student and personnel pay ranges. The budget should also include financial report to show if the institution is profitable. Statements such as cash flow statements, net income, and balance sheet should all be included. The budget must also be flexible enough in case that their projections arent accurate. They should be easily accessible so that managers can routinely check if their performance is above, below, or even on target. To determine if the institution is on track with its budget and strategic plans, they would measure their six categories in their budget to get a better picture of the institutions performance. They are new students, enrollment, cost performance, revenue, net income, and cash flow. This way they would also be able to measure the efficiency of their institution also. The goal for Not-For-Profit Colleges is to provide students with higher education and help them advance in a particular field. Not-For-Profit Colleges are traditional college such as community colleges, state universities, and liberal arts colleges. These institutions gain funding to provide their services from the government subsidy, tuition fees, and donations. All the income that are received is strictly used for institution purposes. Some examples are professors, staff, maintenance, utilities, or even computers that the school needs and student needs. All the money is given back to the institution in some way. The professors hired at a Not-For-Profit College design their own courses and create their own course curriculum and lesson plan. They can provide the education in their courses with their own individual styles and lesson plans. The professors are under the guidance of the Board of Trustees, which is composed of different representatives that make decisions for the college. Not-For-Profit colleges are mainly to provide education for the student who are enrolled in their institution. The classes are usually on a campus in which the student spends a majority of their time at. The board of Trustees focuses on improving their campus for the student. The Board of Trustees is constantly making decisions from an academic, campus, and efficiency perspective in order to provide the best possible service for their students. Not-For-Profit Colleges select their students through a vigorous and selective process. Students usually express interest in attending the college and then the college decides if the student would be a good fit for the college. After being accepted, the student would be able to earn a scholarship to help with the room and board that the college charges. Not-For-Profit Colleges are selective of the students since they strive to serve students who would fit the reputation of the institution. This selective process allow college to focus on the needs of the students that are a good match for the college. From an accounting perspective Not-For-Profit colleges follow the rules of Governmental Accounting Standards Board who is responsible for Generally Accepted Accounting Principles used by the United States. The Governmental Accounting Standards Board issues statements that deal with the accounting principles and financial reporting rules of government and other Not-For-Profit organizations. Like all Not-For-Profit organization, these college contribute without expecting commensurate returns. Their main purpose is to provide education to the students that enroll in their school. Most of their income for these colleges come from the tuitions and fees they receive from their student. Other income comes from donation and government subsidies. When a Not-For-Profit College receives tuition payments and fees in full from students the college is supposed to record it at a gross amount, as any revenue would be recorded. If a student meets certain criterion that allows them to attend a publicly funded not-for-profit institution, tuition may be waived in the form of a tuition waiver. Tuition Waivers are reported as a contra-revenue account reducing the revenue account. If the college has any debts, they are recorded just as businesses record them as the debts are recorded with institutional support expenses. Students may pay for college with scholarships which are essentially amounts contributed for the education of a selected individual. Scholarships are given for a range of reasons including high academic standing, membership in certain societies, or awards. However there are two main sources of scholarships which are an outside donor or the scholarship is awarded by the college itself. If the scholarship is from an outside donor the not-for-profit college simply collects the amount receivable from the donor. If the scholarship is awarded by the college itself the accountant reduces the college’s accounts receivable. This reduction in the accounts receivable is recorded as an expense to education and general student aid. Certain expenses of a not-for-profit college are unrestricted net assets classified as instruction expense, research expense, public service expense, academic support, student services, institutional support, operation and maintenance of plant and student aid. Not-For-Profit Colleges cannot operate on tuition fees alone as all the money is immediately put into the school. Fortunately as a Not-For-Profit organization these colleges may receive governmental subsidies as support revenue. There are two types of government subsidies classified as unrestricted and restricted. Unrestricted subsidies are intended for the college to use in general operations. The Board of Trustees also has the power to decide whether a subsidy is unrestricted. Restricted subsidies can be split into either temporarily or permanently. These subsidies often are given for a certain purpose such as an expansion or special project. The restrictions on these subsidies refer to the amount that can be spent and when it can be spent. Sometimes the government may also provide students with grants, which are similar to scholarships in the sense that they are provided to help students reach their financial needs for school. Government grants can both be state or federal and come from government programs such as Pell or the Federal Supplemental Education Opportunity Grant. Similar to scholarships the college may either distribute the cash to the proper students or receive the amount that is to be distributed. If the college decides to receive the grant then it is recorded as a liability in the â€Å"Grant Funds Held for Students† account. Not-For-Profit colleges usually also have an endowment fund which is used to help finance the operating expenses of the organization. Aside from the general endowment the institution may also have restricted endowments intended for specific purposes such as professorships, scholarships or fellowships. For cash received from permanent endowments it is recorded as a contribution and the income is restricted to student aid. Any income received due to an endowment is temporarily restricted and the cash is meant to be spent on student aid. The other services that a Not-For-Profit College provides are the Auxiliary Services. The Auxiliary Services are the services and amenities of the campus. Examples of such services are residence halls, food services and the college athletic teams. These services are classified under unrestricted revenues and expenses. The total of the accounts from the auxiliary services are reported on the Statement of Activities for the College and subsidiary records are also kept. The Statement of Activities for the Not-For-Profit College will usually list the Revenues combined with Total Net Assets Released from Restrictions for Operations to get the Total Revenues and Reclassifications. The next section is usually the Expenses section followed by any Net Change in Unrestricted Assets, Temporarily Restricted Assets and finally Permanently Restricted Net Assets. The Statement of Activities is then followed by a summary on the Change in Assets for the past year. Even though the main purpose of both For-Profit and Not-For-Profit is the same, the way that they function arent necessary the same. The accounting standards and rules that they follow both are very different. Also the rules that both colleges follow are extremely different. Both colleges have their strength and weaknesses in their way that they serve their students. The student should chose the type of college they want depending on what their needs are. If the student is looking to advance their education they should be looking for a traditional Not-For-Profit College. If they are trying to land a job that has technical skills which are required, then the For-Profit College is a better option.

Legalization Essays - Drug Policy Reform, , Term Papers

Legalization Legalization of marijuana has been a controversial issue in the U.S. for the past several years. The people vs. the federal government is just one of the main debates over legalization. In the past marijuana was required to be grown on most plantations in the southern region. It could be purchased in one ounce packages for only twenty five cents. Further down the time line we find that marijuana is increasingly being used in the inner cities and suburban areas. Marijuana was considers legal in the late 1800's but a bill was passed and marijuana was quickly considered to be illegal. The federal legislation prohibiting marijuana passed at the end of 1937 congressional session was virtually scare enacted. people feared the effects of it and wanted to stop the growth and importation of it. Congress passed the Marijuana Tax Act, which requires all persons who import, manufacture, produce, compound, sell, deal in, and dispense pay a graduated occupational tax. This tax was an attempt to make it harder for dealers of marijuana to make money off the export and import of marijuana. Attempts that he government has made to pass bills that decriminalize marijuana were shot down by legislature and the federal government. A survey taken says that although illegality should be maintained, the penalties for it should be lessened. There is a theory that marijuana stimulates violence, yet it has not been proven as a fact. In several states, such as New Jersey, the marijuana regulations and penalties have been lessened. Governor Cahill, from New Jersey, recommended that criminal penalties for a small 2 possession of marijuana should be reduced by making it a disorderly person offense. Dr. Tod Mikuriya, from the Indian Hemp drug commission, proposed a list of regulations for the control of marijuana if it were to become legal. It stated that possession without intent to sell shall not be considered to be a crime, all growers importers shall be regulated and watched over like a typical industry, public places where marijuana is sold for on premises use shall be licensed like any alcohol serving bar, and determination of the THC potency and purity shall be regulated by the U.S. Drug and Food Administration. Attempts to legalize have also been made by presidential issued commissions. A commission issued by president Nixon researched marijuana and reached a conclusion that it would be okay to decriminalize marijuana. This, was of course, quickly shot down by the president and the congress. Jimmy Carter, another president of the United States, also wanted to legals marijuana. In the present day there are groups such as, NORML (National Organization for the Reform of Marijuana Laws) , that issue petitions and bills to the DEA and federal government that try to persuade the legalization of marijuana. NORML compared marijuana to alcohol and reached a conclusion that alcohol is more lethal than marijuana. Their studies have shown that prolonged use of marijuana causes lack of ingenuity severe bronchitis, and it lessens reaction speed. Alcohol has been named for hundreds of thousands of death in the United States. It causes liver disease, a severe mental and physical dependance, and depression. Marijuana is only 3 psychologically addictive and use of it can be stopped easier than alcohol abuse. Also no deaths have ever been recorded that were accused by the use of marijuana. Marijuana is considered to be a Scheduled I controlled substance. that means that it is considered to be a drug that can be easily abused. NORML has made attempts to get the DEA to reschedule marijuana, but they were rejected. If the opinions of major contributors to the illegal view of marijuana could be changed, marijuana might be legalized. Too many studies and too many federal officials tell us that it is wrong for our country to condone a so called life threatening drug. Legalization of marijuana could bring extra income to the country and also help in the decline of alcohol abusers. If legalization was to happen the united states would only prosper. Reefer Madness Atlantic Monthly; August 1994. Eric Schlosses; p. 45-63 Marijuana Crime and Delinquency Literature; June 1970. Linda Whitlock; p.363-382 Pot Law Experience The Washington Star; May 6, 1975 Lee Johnson; p.A1-A10 Marijuana Alert Peggy Man Copyright: 1985 p.261, 101, 444 International Drug Traffic Edward F. Dolan, Jr. Copyright 1985 p. 85-86

English 101 for Your Future Impossible is Nothing When You Ace Writing

English 101 for Your Future Impossible is Nothing When You Ace Writing English 101 course is inevitable, and it is better to get the most out of it, then to try ignoring its value and procrastinating with writing tasks. Ability to write concise, interesting and adequate regarding the audience papers is priceless in the modern world, and English 101 is a great place to start. Course Mission English 101 aims to make student understand all basics related to writing in English: content, grammar, research, references and even making reviews and adopting texts to the specific audiences. Curriculum Fundamentals English 101 syllabus might vary from college to college, but the basics stay the same. Reading and Researching Books. There will be several literary works during the course, which you will be obligated to read and analyze. The selection of books is mostly based on the combination of classic and literature close to the major field of study. Thus, if your major is history, the book choice for the course will reflect it. Online databases. Though the course covers writing, one of the basic principles of it is to teach students to express their thoughts based on the related materials. To write a strong and interesting paper and to give your story a solid basis, you will have to dig into the various online data storages. Specialized sources. Newspapers, magazines, Facebook pages anything related to your major field of study will come in handy. Some professors give even give a list of public figures, bloggers, groups and pages you have to subscribe to and follow. It will both give you new, up-to-date information and an insight on how successful people and projects express themselves. Analysis It may be hard to believe, but making an analysis and putting the outcomes into writing is the valuable part of the English 101 curriculum. If you pay attention to the assessment rubric for this course, you will find out that it is almost impossible to score more than C without backing up your essay with an in-depth analysis of some data or your personal experience. English 101 teaches you not just to express thoughts and describe facts or events, but to make the most out of them and dig deep. Writing The last but not the least on this list is the writing itself. You will have to produce more than 20 pages of material as the result of the semester and it will take the following forms: Reflective essays. The most famous task of the English 101 course. To score in it, don’t just describe your experience but show how it affected you. In-class writing exercises. Pay extra attention to them, as the final test or final writing task is often based on the. Blog entries. Even if you a techie, an ability to write simple, correct and engaging won’t harm your future, so don’t pull a lazy-bone with this task. Peer reviews. You will have to learn how to assess your classmates’ writings. You will make comments on grammar, style, conclusions and outcomes, the strength of topics, etc. Stay positive and polite, be constructive and never forget to mention what you liked about the paper. 5 Rules for Dealing with English 101 Course without a Flinch Even if you misstep some basic principles when writing one or two papers, it won’t be a big deal. But you should follow these rules to complete your English 101 course without getting into trouble. 1. Practice Makes Perfect If you were not an avid reader in high school, now it is time to immerse yourself in reading some of the classical literature you have always shunned. Also, create English essay 101 outlines and proceed to draft English 101 sample essays based on your experience that mirror the tone of the books you have read. This practice will serve you well for the tasks ahead. 2. Immerse Yourself into English Culture Attend college plays and programs developed by the creative art department. It is free and gives you an opportunity to make fun and useful connections, not only ace your perception of English classics. 3. Use Online Resources Intensely The world is a global village and this means your professor, as well as other reputable educationists, have online materials that extensively cover English 101. Many of these materials include English 101 essay samples and English 101 essay topics which can serve as directions or guidelines for your work. 4. Avoid Plagiarism like the Plague In literary circles, plagiarism is viewed as intellectual theft and should be avoided at all costs. This does not mean you shouldn’t be inspired by the essays or literary works of others. Therefore if you see a story that you like and would want your English 101 final exam essay to be as good as, note and follow the structure used and dont forget about such fine touches as idioms, metaphors and robust data background. 5. Always Ask Questions Generally, educators view students who ask questions as serious individuals who are dedicated to learning more about a subject matter. Well-crafted questions will endear you to your teacher. On the other hand, you can clarify any confusions you may have by simply lifting a finger. Consider English 101 course as a course for which many people would pay significant sums of money nowadays, but they don’t go to college already or yet. People pay hundreds if not thousands of dollars for writing courses which might help them to develop their blogs, write books or just find a better job. Invest yourself, and spoon off cream onwards. Additionally, you can get professional help with writing an essay from English 101 experts at our website.

History 16 Essay Example | Topics and Well Written Essays - 250 words

History 16 - Essay Example The movie specifically dwells on political happenings that were informing the decision making process of the president during the periods of the Cuban Missile Crisis (Kennedy, 45). It is of critical importance to note that the movie â€Å"Thirteen Days† is historically accurate. There are several circumstances captured in the movie that qualifies it for historical accuracy. For instance, the movie depicts one of the periods in history when the president of America, President John F Kennedy met with one of the Soviet ambassadors. This meeting took place at the Justice Department and it is a historical reality. The meeting involved the president and Anatoly Dobrynin ad it took place a certain evening of the 27 October 1962 (Ponting, 37). This makes the movie â€Å"Thirteen Days† historically accurate. It is important to note that the movie may be important to the students in several aspects. It equips the students with knowledge regarding conflict resolution. This is critical in ensuring that each every student becomes well informed in matters dealing with such conflicts in the society. The movie also focuses much on the issue of leadership (Ponting, 53). This is crucial for students since it equips them with the requisite skills and knowledge pertaining to leadership. It sheds more light on how to deal with political unrest relevant to the leaders’ personalities and behavior. This is critical to such students who may have interest of becoming political leaders in

Friedrich A. Hayeks Individualism and Economic Order Summary Essay

Friedrich A. Hayeks Individualism and Economic Order Summary - Essay Example The themes used by the writer indeed became the central ideas around which the entire book, which is actually made up of a collection of writings was written. Four of these basic ideas are summarized below. Facts and Fallacies of Individualism The economist holds a basic idea that individualism, and for that matter social order is neither a fact nor a fallacy but that it is both a true and false. First, the economist writes to associate individualism more to be a social order whereby regardless of the fact that people are expected to behave and react in a certain individualistic manner to meet their economic needs of life, they are at the same time obliged to act according to the larger interest of society. From this perspective, the economist goes on further to give vivid reasons why individualism and for that matter, the social order could be considered to be false. The explanation given is that â€Å"in social matters, one does not adhere to fixed principles but decides each ques tion "on its merits"; that one is generally guided by expediency† (Hayek, 1996, p. 1). Invariably, the writer is implying that no individual would be robotic to economic principles even when those principles deny him food on his table. This is what makes individualism true because people function economically according to the dictates of their conditions. On the other hand, there is a justification given as to why individualism and economic order could be true. With this, the economist explains that â€Å"principles, have a way of asserting themselves even if they are not explicitly recognized but are only implied in particular decisions (Hayek, 1996, p. 1).† In other words, even if a person defies the provisions of economic principles, the core values of these principles remain a fact and thus true. The use of Knowledge in Society In the second theme and basic knowledge explicitly outlined by the economist, he visits the availability of knowledge and the use of it ther eof in modern society. Whiles doing this, the economist related economies to social science by making the assertion that the provisions that make social existence possible form the basis of rational economic order (Gabby, 2005). To this, the economist emphasizes the point that what society really needs to manage its rational economic order is logic. By logic, the economist talks of using common sense presented at the individual stage of getting things worked out for a person. A clear sense, therefore, an endorsement is made by the writer of individualism as a fact by raising the point of logic. The economist further throws light on the fact that the logic needed to make things work out for individual entities within society comes about as a result of making use of available information, and thus knowledge.

Public Examination Should Not Be Abolished Essay Example for Free

Public Examination Should Not Be Abolished Essay While several states are implementing some form of standards-based reform, there is very little empirical evidence to prove that standards, assessment, and high-stakes accountability programs are effective in improving public schools. In many states, such as California, attempts to implement standards-based reform are inconsistently or carelessly aligned with quality research. The following are some of the shortcomings of standards-based reform. 1. Recent reports on the standards-based reform movement in New York suggest that in many schools the careless implementation of standards and assessment may have negative consequences for students. Vague and unclear standards in several subject areas in several states complicate matters and do not serve as concrete standards defining what students should know and be able to do. 3. Top-down standards imposed by the federal or state government are also problematic. They impose content specifications without taking into account the different needs, opportunities to learn, and skills that may be appropriate for specific districts or regions. Table 1: Advantages of SBA compared with external examinations Point Characteristics of SBA Characteristics of Exams Scope Extends the range and diversity of assessment collection opportunities, task types and assessors Much narrower range of assessment opportunities: less diverse assessment; one exam per year Authenticity Assessment done by students own teacher; less possibility of cheating as teacher knows student capabilities; assessments more likely to be realistic Removes assessment entirely from teaching and learning; stressful conditions may lead to students not demonstrating real capacities Validity Improves validity through assessing factors that cannot be included in public exam settings Limits validity by limiting scope of assessment, e. g. difficult to assess interaction skills in exam environment Reliability Improves reliability by having more than one assessment by a teacher who is familiar with the student; allows for multiple opportunities for assessor reflection/standardisation Even with double marking, examiners judgments can be affected by various factors (task difficulty, topic, interest level, tiredness, etc); little opportunity for assessor reflection / review Fairness Fairness is achieved by following commonly-agreed processes, outcomes and standards; teacher assumptions about students and their oral language levels is made explicit through collaborative sharing and discussion with other teachers Fairness can only be achieved by treating everyone the same, i. e. setting the same task at the same time for all students. Feedback Students can receive constructive feedback immediately after the assessment has finished, hence improving learning The only feedback is usually a grade at the end of the course; no opportunities for interaction with assessor; no chance to ask how to improve Positive washback (beneficial influence on teaching and learning) Ongoing assessment encourages students to work consistently; provides important data for evaluation of teaching and assessment practices in general Examination is purely summative, and does not serve any teaching-related purpose; effects on teaching and learning may even be negative; may encourage teaching to the test and a focus on exam technique, rather than outcomes. Teacher and student empowerment Teachers and students become part of the assessment process; collaboration and sharing of expertise take place within and across schools Teachers play little to no role in assessment of their students and have no opportunity to share their expertise or knowledge of their students; students treated as numbers Professional development Builds teacher assessment skills, which can be transferred to other areas of the curriculum Teachers have no opportunity to build their assessment skills; get little or no feedback on how to improve as teachers

Analysis of Satans Speech in in John Miltons Paradise Lost

Analysis of Satan's Speech in Milton's Paradise Lost      Ã‚  Ã‚   John Milton's Paradise Lost is a work of enduring charm and value because of its theological conceptions, its beautiful language, and its "updating" of the epic to the modern world's values. Book II of this epic poem opens with Satan's speech to his minions in hell, proposing war on Heaven itself. In these first 44 lines, Satan is clearly established as epic hero, but at the same time is theologically/morally denounced by the speaker.    This section of the poem opens by establishing Satan's position of power and prestige:    High on a throne of royal state, which far Outshone the wealth of Ormus and of Ind, Or where the gorgeous East with richest hand Show'rs on her kings barbaric pearl and gold, Satan exalted sat, (II. 1-5).    These lines create an aura of awe and majesty for Satan, showing his glory and splendor through material things, while at the same time inferring indirectly that this material show is all that Satan has, rather than real power or value.    After this portrayal of Satan the epic hero in all his magnificence, the speaker (the heavenly muse) is very careful to bring down his image morally, despite the magnificent outward experience. The muse asserts that,    by merit raised To that bad eminence; and from despair Thus high uplifted beyond hope, aspires Beyond thus high, insatiate to pursue Vain war with Heav'n, and by success untaught His proud imaginations thus displayed, (II. 5-10).    The muse is very careful to remind the reader that Satan is in a high position because of his greed, and the high position he has obtained is not a good position t... ...son who uses elevated language well. The speaker's voice is brought forth showing that despite Satan's slick moves, he is the villain, but the reader still feels sympathy for Satan. The speech is a moving one, and certainly accomplishes the task of motivating the denizens of Hell to move against Heaven. It fits the framework of the poem perfectly, showing not only the theological goals of the poem, but also the desire of the poem to "mock" the traditional epic, and to provide a literary work of great beauty and power.    Sources    Fox, Robert C. "The Allegory of Sin and Death in Paradise Lost." Modern Language Quarterly 24 (1963): 354-64. Lewis, C. S. A Preface to Paradise Lost. Rpt. New York: Oxford UP, 1979. Milton, John. Paradise Lost. In John Milton: Complete Poems and Major Prose. Ed. Merritt Y. Hughes. Indianapolis: Odyssey, 1980.

Facilitation of Conditioned Fear Extinction

Neuroscience 134 (2005) 247–260 FACILITATION OF CONDITIONED FEAR EXTINCTION BY D-CYCLOSERINE IS MEDIATED BY MITOGEN-ACTIVATED PROTEIN KINASE AND PHOSPHATIDYLINOSITOL 3-KINASE CASCADES AND REQUIRES DE NOVO PROTEIN SYNTHESIS IN BASOLATERAL NUCLEUS OF AMYGDALA Y. L. YANGa AND K. T. LUb* Institute of Biotechnology, Department of Molecular Biology and Biochemistry, National Chia-Yi University, 300 University Road, Chia-Yi, Taiwan b Department of Life Science, National Taiwan Normal University, 88 Ming-Chow Road, Sec 4, Taipei, Taiwan aKey words: extinction, D-cycloserine, MAPK, PI-3 kinase, amygdala. Abstract—Recent results showed that either systemic or intra-amygdala administration of D-cycloserine, a partial agonist at the glycine modulatory site on the glutamate N-methylD-aspartate receptor facilitates the extinction of conditioned fear. Here we evaluated the role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase in the basolateral nucleus of amygdala on the effect of D-cycloserine.The facilitation effect of D-cycloserine on fear extinction and mitogen-activated protein kinase activation was completely blocked by intra-amygdala administration of mitogen-activated protein kinase inhibitor PD98059 (500 ng/side, bilaterally) or U0-126 (20 M/side, bilaterally). Furthermore, phosphatidylinositol 3-kinase inhibitor (wortmannin, 5. 0 g/side, bilaterally) infused into the basolateral nucleus of amygdala signi? cantly reduced both facilitation effect of D-cycloserine and phosphatidylinositol 3-kinase activation.Intra-amygdala administration of a transcription inhibitor (actinomycin D, 10 g dissolved in 1. 6 l vehicle; 0. 8 l per side) and a translation inhibitor (anisomycin, 125 g dissolved in 1. 6 l vehicle; 0. 8 l per side) completely blocked the facilitation effect of D-cycloserine. Control experiments indicated the blockage by actinomycin D or anisomycin were not due to lasting damage to the basolateral nucleus of amygdala or state d ependency. In addition, none of the active drugs used here altered the expression of conditioned fear.These results suggested that phosphatidylinositol 3-kinase and mitogenactivated protein kinase-dependent signaling cascades and new protein synthesis within the basolateral nucleus of amygdala played important roles in the D-cycloserine facilitation of the extinction of conditioned fear.  © 2005 Published by Elsevier Ltd on behalf of IBRO. *Corresponding author. Tel: 886-2-29333149Ãâ€"234; fax: 886-229312904. E-mail address: [email  protected] ntnu. edu. tw (K. -T. Lu).Abbreviations: ACT DCS, actinomycin D D-cycloserine; ACT SAL, actinomycin D saline; ANI DCS, anisomycin D-cycloserine; ANI SAL, anisomycin saline; BLA, basolateral nucleus of the amygdala; CS, conditioned stimulus; DCS, D-cycloserine; EDTA, ethylenediaminetetraacetic acid; ISI, interstimulus interval; MAPK, mitogen-activated protein kinase; NMDA, N-methyl-D-aspartate; PD DCS, PD98059 D-cycloserine; PD SAL, PD9805 9 saline; PI-3K, phosphatidylinositol 3-kinase; US, unconditioned stimulus; U0 DCS, U0-126 D-cycloserine; U0 SAL, U0126 saline; VEH DCS, vehicle D-cycloserine; VEH SAL, vehicle saline; WH DCS, wortmannin D-cycloserine; WH SAL, wortmannin saline. 0306-4522/05$30. 00 0. 00  © 2005 Published by Elsevier Ltd on behalf of IBRO. doi:10. 1016/j. neuroscience. 2005. 04. 003 Fear conditioning occurs when a previously neutral stimulus (conditioned stimulus) is paired with an aversive stimulus (McAllister and McAllister, 1971).Following such pairing the conditioned stimulus is thought to elicit a state of conditioned fear. This is de? ned in animals by their behavior: freezing, autonomic reactivity, and fear-potentiated startle. A large literature indicates that the basolateral nucleus of the amygdala (BLA) is critically involved in both the acquisition and the expression of conditioned fear (Davis, 2000). Neurotoxic lesions or intra-amygdala infusion of glutamate antagonists into the BLA bl ocks the expression of conditioned fear. In addition, local infusion of N-methyl-D-aspartate (NMDA) speci? c antagonists blocks the acquisition of conditioned fear (Miserendino et al. , 1990; Kim et al. , 1991; Maren et al. , 1996; Gewirtz and Davis, 1997).Synaptic plasticity in this area is thought to underlie the learning process when afferent sensory information elicited by the conditioned stimulus is paired with afferent pain information elicited by the unconditioned stimulus (Fanselow and LeDoux, 1999). Extinction is de? ned as a reduction in conditioned fear when the conditioned stimulus (CS) is presented repeatedly in the absence of the unconditioned stimulus (US). Many studies show that extinction is not the result of forgetting or memory erasure but results from formation of new associations that compete with prior fear-conditioned associations (Falls and Davis, 1995; Davis et al. , 2000). Similar to acquisition, extinction is also blocked by glutamate NMDA receptor antagon ists either given systemically (Cox and Westbrook, 1994; Baker and Azorlosa, 1996; Kehoe et al. 1996) or locally infused into the BLA (Falls and Davis, 1992). The glycine modulatory site of the NMDA receptor provides a critical regulatory role. Whereas direct NMDA agonists may be neurotoxic due to unregulated calcium entry, partial agonists can facilitate glutamatergic NMDA activity in a more limited fashion (Lawler and Davis, 1992; Olney, 1994). Recent results showed that partial agonists acting at the glycine modulatory site of the NMDA receptor, such as D-cycloserine (DCS), enhance learning and memory in several animal models (Thompson and Disterhoft, 1997; Pussinen et al. , 1997; Matsuoka and Aigner, 1996; Land and Riccio, 1999; Walker et al. , 2002; 247 248 Y. L. Yang and K. T.Lu / Neuroscience 134 (2005) 247–260 extinction test, an extinction training and a post-extinction test (see Fig. 1A). Acclimation. On each of 3 consecutive days, rats were placed in the test chamb ers for 10 min and then returned to their home cages. Baseline startle test. On each of the next 2 consecutive days, animals were placed in the test chambers and presented with 30 95-dB startle stimuli at a 30-s interstimulus interval (ISI). Animals whose baseline startle response was 1% of the measurable level were not included in later analysis. Fear conditioning. Twenty-four hours later, rats were returned to the test chambers and after 5 min were given the ? rst of 10 light-footshock pairings.The shock (US) was delivered during the last 0. 5 s of the 3. 7 s light (CS). The average intertrial interval was 4 min (range 3–5 min) and the shock intensity was 0. 6 mA. Pre-extinction test. Twenty-four hours after fear conditioning, rats were returned to the test chambers and 5 min later presented with 30 startle-eliciting noise bursts (95 dB, 30 s ISI). These initial startle stimuli were used to habituate the startle response to a stable baseline prior to the light-noise test tr ials that followed. Thirty seconds later a total of 20 startle-eliciting noise bursts were presented, 10 in darkness (noise alone) and 10 3. 2 s after onset of the 3. s light (light-noise) in a balanced, irregular order at a 30-s ISI. Percent fear-potentiated startle was computed as [(startle amplitude on light-noise noise-alone trials)/noisealone trials] 100. Rats were then divided into equal size groups of comparable mean levels of percent fear-potentiated startle. Rats with less than 50% fear-potentiated startle during the pre-extinction test were not used. Extinction training. Extinction training (cue exposure) is de? ned as the repetitive exposure to the CS cue (light) in the absence of the US (shock). Twenty-four hours after the preextinction test, rats were returned to the test chamber. After 5 min, they were presented with 30, 3. s light exposures at a 30-s ISI. Context control groups (context exposure) remained in the test cages for the same amount of time but did not recei ve light presentations. Extinction training was performed for varying numbers of consecutive days (2 days for experiment 1 and 1 day for subsequent experiments). Post-extinction test-1. Twenty-four hours after the last extinction training, rats were returned to the test chamber. After 5 min, they were presented with 30 95-dB leader stimuli for a habituated startle baseline. This was followed by a total of 60 startle-eliciting noise bursts, 30 in darkness (noise alone) and 30 presented 3. 2 s after onset of the 3. s light (light-noise) in a balanced, irregular order at a 30-s ISI. Results were evaluated the same way as pre-extinction test. Post-extinction test-2. Twenty-four hours after the extend extinction training period, rats were returned to the test chamber and process the post-extinction test described above. Fear-potentiated startle test. Twenty-four hours after fear conditioning, rats were returned to the test chamber and testing for fear-potentiated startle using the post-e xtinction test-1 described above. Ledgerwood et al. , 2003; Richardson et al. , 2004). In addition, ( )-HA966, a competitive antagonist at the glycine regulatory site on the NMDA receptor, reversed the DCS effect (Walker et al. , 2002).Clinical studies have shown that DCS can sometimes enhance implicit memory and improve cognition in patients with Alzheimer’s disease (Schwartz et al. , 1996; Tsai et al. , 1998, 1999). It can also counter cognitive de? cits in schizophrenia (Javitt et al. , 1994; Goff et al. , 1999). Furthermore, systemic administration of DCS also proved to facilitate extinction of conditioned fear (Walker et al. , 2002; Ledgerwood et al. , 2003, 2004; Ressler et al. , 2004). Numerous signaling cascades including mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI-3K) and calcineurin, are involved in the extinction of conditioned fear (Lu et al. , 2001; Lin et al. , 2003).Similar mechanisms may also be involved in the facilitation effec t of DCS. This study was designed to clarify the relationship between amygdaloid NMDA receptors, MAPK and PI-3K signal cascades on the extinction of conditioned fear. EXPERIMENTAL PROCEDURES Animals Adult male Sprague–Dawley (SD) rats (obtained from the animal center of National Taiwan University Taipei, Taiwan) weighing between 250 and 350 g were used. Animals were housed in groups of four rats in a temperature (24  °C) -controlled animal colony with continuous access to food and water. Rats were kept on a 12-h light/dark cycle with lights on at 07:00 h. All behavioral procedures took place during the light cycle.All procedures were conducted in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals and the guidelines set forth by the Institutional Animal Care and Use Committee at the National Taiwan Normal University. In all experimental procedures involving animals, all efforts were made to minimize pain and the number of animals u sed. Surgery All surgeries were carried out under sodium pentobarbital (50 mg/ kg, i. p. ) anesthesia. Once anesthetized, the rat was placed in a Kopf stereotaxic instrument, the skull was exposed, and 22 gauge guide cannula (model C313G, Plastic-one Products, Roanoke, VA, USA) were implanted bilaterally into the BLA (AP, 2. ; DV, 9. 0, ML, 5. 0 from bregma (Paxinos and Watson, 1997)). Size 0 insect pins (Carolina Biological Supply, Burlington, NC, USA) were inserted into each cannula to prevent clogging. These extended about 2 mm past the end of the guide cannula. Screws were anchored to the skull and the assembly was cemented in place using dental cement (Plastic-one Products). Rats received an antibiotic (penicillin) once every day for the ? rst 3 days after the surgery to reduce the risk of infection. General behavioral procedures Fear conditioning was measured using the potentiated startle paradigm (Cassella and Davis, 1986; Lu et al. , 2001; Walker et al. , 2002).The rats were trained and tested in a startle chamber (San Diego Instruments, San Diego, CA, USA) in which cage movement resulted in the displacement of an accelerometer. Startle amplitude was de? ned as peak accelerometer voltage within 200 ms after startle stimulus onset. The behavioral procedures common to all experiments consisted of an acclimation phase, a baseline startle test phase, a fear conditioning phase, a pre- Drug injection DCS (Sigma) was freshly dissolved in saline. DCS (15 mg/kg, i. p. ) or saline was injected intraperitoneally 15 min prior to extinction training with a 26 gauge injection needle connected to a 1 ml syringe (Walker et al. , 2002; Ledgerwood et al. , 2003) (experiments 1– 8).MAPK inhibitor PD98059 (500 ng in 1 l of 20% DMSO; Calbiochem) (Lu et al. , 2001) or U0-126 (50 ng/side; Sigma) (Lin et al. , 2003) or 20% DMSO was infused into the BLA Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 249 Fig. 1. Systemic administration of DCS accelerate d extinction of conditioned fear. (A) Timeline of behavioral procedures for experiment 1. (B) Percent fear-potentiated startle measured 24 h before (pre-extinction test) and 24 h after extinction training (post-extinction test). Rats in each group were treated with either DCS or saline prior to a single session of extinction training. (C) To test for toxicity, after 24 h all animals of experiment 1 were retrained.They were tested for fear-potentiated startle response in the absence of drugs 24 h later (fear-potentiated startle test) (values are mean SEM, * P 0. 05 versus control group; # P 0. 05 versus the group with 1 day extinction and saline injection). 250 Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 10 min prior to saline or DCS injection (experiments 2 and 8). PI-3K inhibitor (wortmannin, 5 g/side) (Lin et al. , 2003) or vehicle was administrated to the BLA 10 min prior to saline or DCS injection (experiment 3). Transcription inhibitor actinomycin D (10 g d issolved in 1. 6 l vehicle; 0. 8 l per side) or translation inhibitor (anisomycin, 125 g dissolved in 1. 6 l vehicle; 0. 8 l per side) or vehicle (Lin et al. 2003) was administrated to the BLA 10 min prior to DCS or saline injection (experiment 4) or 25 min prior to fear-potentiated startle test (experiment 6). In the control experiment, PD98059, U0-126, wortmannin, actinomycin D, and anisomycin were injected 25 min prior to the fear-potentiated startle test. Injections were made through 28-gauge injection cannula (model C313I, Plastic-one Products) connected to a Hamilton micro-syringe via polyethylene tubing. Infusion speed was 0. 25 l/ min. The total volume of injection was 0. 8 l per side. Western blot analysis Animals were killed by decapitation 10 min after extinction training. The lateral and basolateral subregions of the amygdala were collected and sonicated brie? y in ice-cold buffer: 50 mM Tris–HCl (pH 7. ), 50 mM NaCl, 10 mM EGTA, 5 mM EDTA, 2 mM sodium pyrophospha te, 4 mM para-nitrophenylphosphate, 1 mM sodium orthovanadate, 1 mM phenylmethylsulfonyl ? uoride (PMSF), 20 ng/ml leupeptin, and 4 ng/ml aprotinin. Following sonication, the soluble extract was obtained after pelleting the crude membrane fraction in a centrifuge at 50,000 g at 4  °C. Protein concentration in the soluble fraction was then measured using a Bradford assay with bovine serum albumin as the standard. Equivalent amounts of protein for each sample were resolved in 10% sodium dodecyl sulfate (SDS)–polyacrylamide gels, blotted electrophoretically to PVDF membranes and blocked overnight in 5% skim milk (Cell Signaling Technology, Inc. , USA).Blots were incubated with antiphospho-ERK antibody (New England Biolabs, USA), anti-ERK antibody (BD Transduction Laboratories, USA), anti-phospho-Akt antibody (New England Biolabs) or anti-pan-Akt (BD Transduction Laboratories). Band detection was performed with an enhanced chemiluminescence Western blotting analysis system (RPN 2108; Amersham International, Amersham, UK). fear-potentiated startle during the pre-extinction test. The ? nal 30 rats were assigned into ? ve groups of six animals based on their level of fear-potentiated startle in the preextinction test. Twenty-four hours after the pre-extinction test, each rat received 1 or 2 consecutive days of extinction training with DCS (15 mg/kg, i. p. ) or saline. Saline or DCS was injected 15 min prior to the extinction training.An additional control group was tested 2 days after the pre-extinction training without intervening exposures to visual CS. Fig. 1B shows that DCS accelerated extinction of conditioned fear. A two way ANOVA for differences in treatment (DCS vs saline) and days (one or two extinction sessions) between-subjects indicated a signi? cant treatment effect (F(1,20) 9. 02) and a signi? cant treatment days interaction (F(2,20) 6. 68). Thus, the reduction of fear-potentiated startle after 1 day of extinction training was greater in the gr oup that received DCS than in the group that received saline (Fig. 1B). Individual comparisons between DCS- and saline-treated groups indicated signi? ant differences after 1 day of extinction sessions (t(10) 3. 86). Previous studies have shown that lesions of the BLA block expression of fear-potentiated startle (Campeau and Davis, 1995). DCS may have toxic effect on BLA, and resulting misinterpretation of its facilitation effects on extinction. To test for toxicity, all animals of experiment 1 were retrained and tested 24 h later. Under these conditions, animals previously injected with DCS or saline showed a signi? cant fear-potentiated startle (Fig. 1C). Thus, the facilitation effect of DCS observed during the post-extinction test 1 appeared to result from the acute drug effect rather than from a more permanent, perhaps toxic, action of DCS.Experiment 2: intra-amygdala infusion of MAPK inhibitors blocked the facilitation of extinction by DCS To test the possible role of MAPK-depe ndent signaling cascade in the DCS-enhanced effect on the extinction of condition fear, 48 rats received fear conditioning, extinction training, and testing for fear-potentiated startle. Initially, 58 rats were used, but 10 of them were excluded. Rats were randomly assigned to six different groups and received one of the following treatments: vehicle saline (VEH SAL), vehicle DCS (VEH DCS), PD98059 DCS (PD DCS), U0-126 DCS (U0 DCS), PD98059 saline (PD SAL) or U0-126 saline (U0 SAL). The MAPK inhibitors, PD98059, and U0-126 (or vehicle) were administrated to the BLA 10 min prior to the injection with DCS or saline. Animals were then returned to their cage.Fifteen minutes after injection, animals were subjected to a single session of extinction training. Previously, we show that a single day of extinction training with cue exposure led to about 35% decrease in fear-potentiated startle, whereas 2–3 days of extinction training led to near complete extinction (Lu et al. , 2001; Wa lker et al. , 2002). We concluded that the acceleration of extinction is best detected after a single session of extinction training. As shown in Fig. 2, DMSO, PD98059 (500 ng/side, bilaterally), or U0-126 (20 nM/per side, bilaterally) was given 10 min prior to saline or DCS injection; rats were returned to their cages for 30 min before a single HistologyRats were overdosed with chloral hydrate and perfused intracardially with 0. 9% saline followed by 10% formalin. The brains were removed and immersed in a 30% sucrose-formalin solution for at least 3 day. Coronal sections (30 M) were cut through the area of interest, stained with Cresyl Violet, and examined under light microscope for cannula placement. Animals with misplaced cannula were not included in later analysis. Statistical analysis The mean startle amplitude across the 30 noise alone and 30 light-noise trials during the pre- and post-extinction tests was calculated for each animal. All results were analyzed using a score of percent fear-potentiated startle, as de? ned in the post-extinction tests above.ANOVA on scores was the primary statistical measure. Between-group comparisons were made using two-tailed t-tests for independent samples. The criterion for signi? cance for all comparisons was P 0. 05. RESULTS Experiment 1: systemic administration of DCS accelerated extinction of conditioned fear This experiment assessed the facilitation effect of DCS on different amounts of extinction training. Initially, 35 rats were used. Five were excluded for showing less than 50% Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 251 Fig. 2. Intra-amygdala infusion of MAPK inhibitors blocked facilitation effect of DCS on extinction. (A) Timeline of behavioral procedures for experiment 2. B) Cannula was placed in the BLA. Percent fear-potentiated startle measured 24 h before (pre-extinction test) and 24 h after extinction training (post-extinction test). Rats in each group underwent VEH SAL, VEH DCS, PD DCS, U0 DCS, PD SAL, or U0 SAL prior to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs (values are mean SEM, * P 0. 05 versus VEH SAL group; # P 0. 05 versus VEH DCS group). (C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). 252 Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 session of extinction training.Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs. Results showed that there was a signi? cant overall difference between treatments (F(5,42) 11. 81). Fig. 2 shows that administration of DCS facilitated extinction of conditioned fear (VEH DCS) compared with the control group (VEH SAL) (t(14) 3. 12, P 0. 05). This effect was blocked by co-administration of MAPK inhibitor PD98059 (PD DCS) or U0-126 (U0 DCS) (t(14) 3. 08, P 0. 05 and t(14) 3. 29, P 0. 05, respectively) compared wit h the control (VEH DCS), treated with PD98059 only (PD SAL) or U0-126 only (U0 SAL) did not affect extinction (t(14) 0. 7 and t(14) 0. 36, respectively). These results indicated that the MAPK dependent signaling cascade most likely mediated the facilitation effect of DCS. Experiment 3: intra-amygdala infusion of the PI-3K inhibitor blocked facilitation of extinction by DCS Previous ? ndings have shown that PI-3K inhibitors retard acquisition in a variety of learning paradigms (Lin et al. , 2003). To evaluate the possible role of PI-3K signaling cascade in the DCS enhancement of extinction of conditioned fear, 32 rats received fear conditioning, extinction training, and testing for fear-potentiated startle. Although 38 rats were used initially, six were excluded.They were then randomly assigned to four different groups and received one of the following treatments: VEH SAL, VEH DCS, wortmannin DCS (WH DCS) and wortmannin saline (WH SAL). The PI-3K inhibitor (wortmannin, 5 g/side, bila terally) was infused to the BLA 10 min prior to the injection of saline or DCS. Then rats were returned to their cages for 15 min before being subjected to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs. Results showed that there was a signi? cant overall difference between treatments (F(4,28) 12. 17). As shown in Fig. 3, the facilitation effect of DCS (VEH DCS) on extinction was blocked by co-administration of PI-3K inhibitor (WH DCS) (t(14) 2. 98, P 0. 05).With the single extinction training session used in this experiment, this dose of wortmannin alone (WH SAL) at this dose had no effect on the extinction of fear-potentiated startle compared with control group (VEH SAL) (t(14) 0. 19). These results suggest that the PI-3K signaling cascade was involved in the DCS facilitation of extinction. Experiment 4: DCS enhanced the extinction training induced MAPK and PI-3K phosphorylation According t o the results of the above experiments, the DCS facilitation effect on extinction was prevented by coadministration of MAPK or PI-3K inhibitor. Previous studies have shown that infusion of these same inhibitors blocks extinction (Lu et al. , 2001; Lin et al. , 2003). Therefore, these treatments in conjunction with DCS must result in no extinction and resulting misinterpretation of its blockage effects on DCS.To show the MAPK and PI-3K signaling pathways are essential for the facilitation effect of DCS, we used Western blot to evaluate the DCS effect on the extinction training induced MAPK and PI-3K phosphorylation. Additional amygdala-cannulated rats received fear conditioning, extinction training, and testing for fear-potentiated startle. Then PD98059 or wortmannin was infused to the BLA 10 min prior to the injection of saline or DCS. Rats were returned to their cages. Fifteen minutes after DCS or saline injection, animals were subjected to a single session of extinction training. Animals were killed by decapitation 10 min after extinction training.The lateral and basolateral sub-regions of the amygdala were tested with Western blot analysis. Compared with control group, MAPK phosphorylation was signi? cantly elevated in BLA after extinction training (Fig. 4A, lane 2). Administration of DCS enhanced the effect of extinction training on MAPK phosphorylation (Fig. 4A, lane 3). The MAPK inhibitor PD98059 blocked the effect of DCS (Fig. 4A, lane 4). In addition, we measured the state of Akt phosphorylation as an index of PI-3K activity (Lin et al. , 2001). Fig. 4B showed that administration of DCS enhanced the effect of extinction training on Akt phosphorylation (Fig. 4B, lane 3). The PI-3K inhibitor, wortmannin, blocked the enhancement effect of DCS (Fig. 4b, lane 4).These results raise the possibility that DCS enhancement effect of extinction of conditioned fear is mediated by the amygdaloid MAPK and PI-3K dependent signaling cascades. Experiment 5: intra-amygd ala infusion of the transcription inhibitor or translation inhibitor blocked DCS facilitation of extinction The MAPK pathway participates in the synthesis of proteins important for the long-term stabilization and storage of fear memories. According to the result of experiment 2, the facilitation effect of DCS on extinction is mediated by the MAPK dependent signaling cascade. We predicted that the facilitation effect of DCS required new protein synthesis in the BLA.To test this hypothesis, 48 rats received fear conditioning, extinction training, and testing for fear-potentiated startle. Initially, 56 rats were used but eight of them were excluded. Rats were then randomly assigned to six different groups and received one of the following treatments: VEH SAL, VEH DCS, actinomycin D DCS (ACT DCS), anisomycin DCS (ANI DCS), actinomycin D saline (ACT SAL), and anisomycin saline (ANI SAL). Transcription inhibitor (actinomycin D, 10 g dissolved in 1. 6 l vehicle; 0. 8 l per side) and transl ation inhibitor (anisomycin, 125 g dissolved in 1. 6 l vehicle; 0. 8 l per side) were administered to the BLA 10 min prior to saline or DCS injection. Then rats were returned to their cages. Fifteen minutes later, nimals were subjected to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs. Results showed that there was a significant overall difference between treatments (F(5,42) 10. 17). As shown in Fig. 5, actinomycin D and anisomycin completely blocked the facilitation effect of DCS (t(14) 3. 11 and t(14) 2. 96, respectively) compared with the VEH DCS group. With a single extinction training session used in this experiment, actinomycin alone (ACT SAL) or anisomycin alone (ANI SAL) did not affect the extinction of fear-potentiated startle compared with control Y. L. Yang and K. T.Lu / Neuroscience 134 (2005) 247–260 253 Fig. 3. Intra-amygdala infusion of the PI-3K inhibitor blocked the fa cilitation effect of DCS on extinction. (A) Timeline of behavioral procedures for experiment 3. (B) Cannula was placed in the BLA. Percent fear-potentiated startle measured 24 h before (pre-extinction test) and 24 h after (post-extinction test) extinction training. Rats in each group were treated with VEH SAL, VEH DCS, WH DCS, or WH SAL prior to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs (values are mean SEM, * P 0. 05 versus VEH SAL group). C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). 254 Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 (VEH SAL) (t(14) 0. 88 and t(14) 0. 48, respectively). These results suggest that new protein synthesis within the BLA played an important role in DCS facilitation of extinction of conditioned fear. Experiment 6: the disruptive effect of intra-amygdala infusion of actinomycin D and anisomy cin was not attributed to lasting damage to the amygdala The active drugs used in the above experiments may have toxic effect within the amygdala. Previous work shows that infusion of PD98095 (Lu et al. , 2001) or wortmannin (Lin et al. 2003) into BLA did not appear to cause permanent impairment of amygdala function. To test for possible toxic effects of actinomycin D and anisomycin on the BLA, all animals of experiment 5 received an additional 2 days of drug free extinction training followed 24 h later by testing. Under these conditions, rats previously treated with actinomycin D (ACT DCS-treated group and ACT SALtreated group) or anisomycin (ANI DCS- and ANI SALtreated group) showed a signi? cant reduction of fearpotentiated startle between post-extinction test 1 and post-extinction test 2 (t(7) 3. 08 and t(7) 3. 32 for the ACT DCS-treated group and ACT SAL-treated group respectively) and (t(7) 2. 96 and t(7) 3. 1 for the ANI DCStreated group and ANI SAL-treated group respectively ) (Fig. 6B). Thus, the blockage of extinction observed during post-extinction test 1 appeared to result from an acute drug effect rather than from a more permanent and perhaps toxic action, of actinomycin D or anisomycin. Previous studies have shown that lesions of the BLA block fear-potentiated startle (Campeau and Davis, 1995), an outcome opposite from that obtained with infusion of actinomycin D or anisomycin. It is also important to note that actinomycin D or anisomycin may have long-term toxicity within the BLA. The extinction of fear would look the same as a gradual loss of ability to express or relearn fear.Experiment 7: the disruptive effect of intra-amygdala infusion of actinomycin D and anisomycin was not attributed to state dependency To evaluate the contribution of state-dependency effects to the results obtained in experiment 6, additional amygdala-cannulated rats were tested for extinction in a drug-free state and after receiving the same compound that they had receive d during extinction training. Results showed that there was a signi? cant overall difference between treatments in post-extinction test 2 (F(2,21) 32. 16). These results are shown in Fig. 7. Rats infused with actinomycin or anisomycin before postextinction test 2 showed a slight, but non-signi? cant, decrease in fear-potentiated startle from post-extinction test 1 to post-extinction test 2. For control rats (n 8), fear-potentiated startle was signi? cantly lower during post-extinction test 2 than post-extinction test 1 (t(7) 2. 455; P 0. 05). The lost of fear-potentiated startle in both groups probably re? cted incidental extinction produced by the 30 non-reinforced CS presentations of post-extinction test 1. The failure of rats infused before Fig. 4. MAPK and PI-3K inhibitors blocked extinction training activation of MAPK and PI-3K. (A) Representative Western blots and densitometric analysis of the activation of MAPK in the BLA under different treatments (values are mean SEM, * P 0 . 05 versus VEH SAL group). (B) Representative Western blots and densitometric analysis Akt phosphorylation as an index of PI-3K activity in the BLA under different treatments (values are mean SEM, * P 0. 05 versus VEH DCS group). Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 255 Fig. 5.Intra-amygdala infusion of the transcription inhibitor or translation inhibitor blocks the facilitation effect of DCS on extinction of conditioned fear. (A) Timeline of behavioral procedures for experiment 5. (B) Cannula was placed in the BLA. Percent fear-potentiated startle measured 24 h before (pre-extinction test) and 24 h after (post-extinction test 1) extinction training. Rats underwent treatment with VEH SAL, VEH DCS, ACT DCS, ANI DCS, ACT SAL, or ANI SAL prior to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs (values are mean SEM, * P 0. 05 comparing with the VEH SAL group; # P 0. 05 compared with the VEH DCS group). C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). 256 Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 Fig. 6. The disruptive effects of intra-amygdala infusion of actinomycin D and anisomycin on extinction were not attributed to lasting damage to the BLA. (A) Timeline of behavioral procedures for experiment 6. The same animals used in experiment 3 were subjected for two more trials of extinction training. (B) Twenty-four hours after the last extinction training, animals were tested for fear-potentiated startle in the absence of drugs (post-extinction test-2) (values are mean SEM, * P 0. 05 versus the corresponding post-extinction test-2). esting with the transcription and translation inhibitors before testing to show a loss of fear-incidental extinction suggested that state dependency was not a major factor in the effects of actinomycin D and anisomycin. Experiment 8: effect of pretest PD98059, U0-126, wortmannin, actinomycin, and anisomycin administration on fear-potentiated startle This experiment was designed to evaluate whether the effect of the active drugs used has had a secondary effect on fear itself or on CS processing. For example, if MAPK inhibitor U0-126 reduced CS-elicited fear, this might attenuate extinction by decreasing the discrepancy between CS predictions and what actually occurred. If actinomycin D or anisomycin interfered with visual processing, this might block extinction produced by non-reinforced exposures to the visual CS.To evaluate these possibilities, 42 amygdala-cannulated rats received acclimation, baseline startle test, and fear conditioning. Initially, 50 rats were used, but eight of them were excluded. After 24 h, rats were infused with PD98059, U0-126, wortmannin, actinomycin, and anisomycin. At 25 min after the infusions, rats were tested for fear-potentiated startle. As shown in Fig. 8, none of the active drugs we used here sig ni? cantly in? uenced fearpotentiated startle (F(6,35) 0. 993). Thus, it is unlikely that these drugs in? uenced extinction by increasing fear or by disrupting CS processing. Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 57 Fig. 7. The disruptive effect of intra-amygdala infusion of actinomycin D and anisomycin were not attributed to state dependency. (A) Timeline of behavioral procedures for experiment 7. (B) Cannula was placed in the BLA. Percent fear-potentiated startle measured 24 h before (pre-extinction test), 24 h after (post-extinction test 1), and 48 h after (post-extinction test 2) extinction training. Rats in each group underwent VEH SAL, ACT DCS, or ANI DCS prior to a single session of extinction training and prior to post-extinction test 2. Animals were tested for fear-potentiated startle in the absence of drugs (values are mean SEM, * P 0. 05). C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). 258 Y. L. Y ang and K. T. Lu / Neuroscience 134 (2005) 247–260 Fig. 8. Effect of pretest PD98059, U0-126, wortmannin, actinomycin, and anisomycin administration on fear-potentiated startle. (A) Timeline of behavioral procedures for experiment 8. (B) Cannula was placed in the BLA. Percent fear-potentiated startle was measured 24 h after fear conditioning. Rats were treated with DMSO, PD98059 (PD), U0-126 (U0), wortmannin (WH), vehicle (VEH), actinomycin (ACT), or anisomycin (ANI) 25 min prior to the fear-potentiated startle test (values are mean SEM). C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). DISCUSSION We build on the previous ? ndings that DCS facilitated extinction of conditioned fear (Walker et al. , 2002; Ledgerwood et al. , 2003, 2004; Ressler et al. , 2004). Here, we show for the ? rst time that the DCS effect was prevented by co-administration of MAPK, PI-3K, transcription, and translation inhibitors. Control experiments indica ted that the blocking effects of actinomycin D and anisomycin on extinction were not due to lasting damage to the BLA or state dependency. In addition, none of active drugs we used in this study altered the expression of conditioned fear.These results suggest that PI-3K and MAPK-dependent signaling cascades and de novo protein synthesis within the BLA were important for DCS facilitation. Early behavioral studies by Pavlov (1927) and Konorski (1948) de? ned extinction as an active process involving formation of new inhibitory associations as opposed to forgetting previously conditioned associations. Numerous studies since have con? rmed and elaborated these early ? ndings (reviewed in Falls and Davis, 1995; Davis et al. , 2000). It is now well accepted that extinction occurs with repeated presentation of a CS in the absence of the pre- Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 259 viously paired US.This reduces the conditioned response elicited by the CS. In co ntrast to forgetting which implies the passive loss of memory, extinction implies active formation of new inhibitory associations competing with and overpowering original excitatory associations. Evidence is growing that extinction may involve circuits and use mechanisms of synaptic plasticity similar to those of conditioned fear learning (Falls and Davis, 1992; Cox and Westbrook, 1994; Baker and Azorlosa, 1996; Davis et al. , 2000). NMDA-dependent synaptic plasticity appears to mediate many forms of active learning (Morris, 1989; Staubli et al. , 1989; Flood et al. , 1990; Collinridge and Bliss, 1995).It is likely that conditioned fear learning depends on CS–US pairing mediated by NMDA receptors within the BLA (Miserendino et al. , 1990; Fanselow and LeDoux, 1999). Extinction also appears to require active, NMDA-dependent learning within the amygdala. This was demonstrated by blockage of extinction by microinjections of APV into the BLA in both fear-potentiated startle (Fall s and Davis, 1992) and freezing paradigms (Lee and Kim, 1998). Furthermore, systemic administration of a different NMDA antagonist, MK801, blocks the extinction process in a range of different learning paradigms (Cox and Westbrook, 1994; Baker and Azorlosa, 1996; Kehoe et al. , 1996).Recently, DCS, a partial agonist acting at the strychnine-insensitive glycine-recognition site of the NMDA receptor complex, has repeatedly been shown to facilitate learning in various cue and context association paradigms (Monahan et al. , 1989; Flood et al. , 1992; Thompson and Disterhoft, 1997). Walker et al. (2002) reported the ? rst evidence that DCS facilitates extinction of learned fear. Since then, further studies con? rmed and elaborated this early ? nding (Ledgerwood et al. , 2003, 2004; Ressler et al. , 2004). These studies reported that DCS is more effective at facilitating extinction when given after extinction training, rather than before. They interpret these ? dings as evidence that DCS facilitates the consolidation of a new memory acquired during extinction. It is important to note that although some studies have shown DCS to be effective in improving memory impairment due to Alzheimer’s disease (Schwartz et al. , 1996; Tsai et al. , 1999) and schizophrenia (Javitt et al. , 1994; Goff et al. , 1999), other studies found little or no improvement (Tsai et al. , 1998; van Berckel et al. , 1999). This may be related to the fact that acute treatment with DCS may have a more pronounced facilitation than chronic treatment (Quartermain et al. , 1994; Ledgerwood et al. , 2003; Richardson et al. , 2004). Ledgerwood et al. (2003, 2004) reported that DCStreated animals fail to exhibit reinstatement effects.That DCS enhances extinction may be through some processes different from extinction induced by repeat representation of CS. Lin et al. (2003) investigated the similarities and differences between consolidation of conditioning and consolidation of extinction. They fo und that both processes depend on activation of NMDA receptors, PI-3K, MAPK, and require synthesis of new proteins within the amygdala. They also found that different characteristics show differential sensitivity to the transcription inhibitor actinomycin D. Our results were consistent with the model that the extinc- tion process involved active learning of new inhibitory associations.Here we showed that DCS facilitation of extinction could be blocked by actinomycin D and anisomycin. These seemingly con? icting results could be attributable to our extinction protocol. Our protocol resembled betweensession extinction, presumably corresponding to long-term extinction memory. In addition, we used DCS to facilitate the extinction process and tested the animals in a drug free condition. Acquisition or consolidation of long-term memory requires activation of protein kinase, transcription of genes, new protein synthesis, and synapse formation (Schafe and LeDoux, 2000). Similar mechanisms w ere involved in the DCS facilitation of extinction. The DCS activated NMDA receptors, resulted in Ca2 in? x into the cell, and led to the PI-3K and MAPK activation. Activated MAPK can translocate to the nucleus, subsequently activating transcription factors to promote gene transcription and new protein synthesis. Thus, combinations of drugs and extinction training may weaken or erase original memory. There is increasing evidence that learning of CS–US associations involves synaptic plasticity within the BLA, leading to differential activation of this circuit by sensory afferents (Davis, 1997; Rogan et al. , 1997; Lee and Kim, 1998; Fanselow and LeDoux, 1999). Our results suggested that the extinction of conditioned fear also involved NMDA-dependent plasticity, but speci? inhibitory circuits may be activated by extinction learning. We hypothesize that this newly activated inhibitory circuit would oppose conditioned excitatory pathways normally leading to activation of the cent ral nucleus of the amygdala, resulting in the elicitation of fear responses. CONCLUSION This may be the ? rst study to show that PI-3K and MAPKdependent signaling cascade and de novo protein synthesis within the BLA were essential to the DCS facilitation of the extinction of conditioned fear. Acknowledgments—The work was supported by grants from the National Science Council (NSC 90-2320-B-003-007, NSC 902320-B-006-038, NSC 93-2320-B-003-003).Our gratitude (also) goes to the Academic Paper Editing Clinic, NTNU. REFERENCES Baker J, Azorlosa J (1996) The NMDA antagonist MK-801 blocks the extinction of Pavlovian fear conditioning. Behav Neurosci 110:618–620. 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