Bio95hfc Tutorial Experience-Based Brain Development – Causes & Consequence Prof. Takao K.

Hensch Contact: Dept of Molecular & Cellular Biology (FAS) Dept of Neurology (Children's Hospital, HMS) Center for Brain Science Harvard University 7 Divinity Ave (Sherman Fairchild 263) Cambridge, MA 02138 USA Tel: 617-384-5882 (MCB) / 617-919-4650 (Children’s) e-mail: hensch@mcb.harvard.edu Course description: At no time in life does the surrounding environment so potently shape brain function as in infancy and early childhood. This course integrates molecular/cellular biology with systems neuroscience to explore biological mechanisms underlying critical periods in brain development. Understanding how neural circuits are sculpted by experience will motivate further consideration of the social impact on therapy, education, policy, and ethics. Course prerequisites: LS 1a, MCB 80, and permission of the instructor. Limited enrollment: 12-15 students. Class location: BioLabs 1079, 16 Divinity Ave, Cambridge MA 02138 Meeting time: Tuesday, 2-4pm (except where indicated) until May 2008

Topics & Readings (brief) Section 1: Core concepts A. Neuronal plasticity & competition <09.18.07> Functional Plasticity: Hebb synapses, LTP/LTD, homeostasis Hensch, T.K. Critical Period Regulation. Annu. Rev. Neurosci. 27: 549-579 (2004). Hensch, T.K. Critical period plasticity in local cortical circuits. Nat. Rev. Neurosci. 6: 877-888 (2005). Hensch, T.K. & Fagiolini, M., eds. Excitatory-inhibitory balance: Synapses, Circuits, Systems (Kluwer Academic Publishing, New York) (2004). <09.27.07> Structural plasticity (guest: J. Lichtman, MCB) NOTE: this session will be held on a Thursday from 1-3pm in SF177 B. Brain maps & timing <10.02.07> Visual system <10.09.07> Barn owl tectum <10.16.07> Birdsong / Human Language <10.23.07> Auditory cortex <10.30.07> Imprinting / anxiety <11.06.07> no class (US Society for Neuroscience meeting) <11.13.07> no class (NINDS BlueSky meeting) <11.20.07> Human cognitive development (guest: E. Spelke, Dept. Psychology) <11.27.07> Human cognitive development (guest: C. Nelson, Children’s Hospital) Section 2: Critical Period Mechanisms A. Induction: Excitatory-Inhibitory Balance <12.04.07> NMDA-R signaling <12.11.07> GABA-R signaling <12.18.07> no class – Happy Holidays! ------------------------------ Inter-session ----------------------------

B. Expression: Structural Plasticity <01.29.08> axons, spines <02.05.08> Intracellular signaling (protein synthesis, CREB, tPA) C. Consolidation: Brakes on plasticity <02.12.07> Extracellular Matrix (peri-neuronal nets / myelin) <02.19.08> Epigenetics (guest: TBA) <02.26.07> no class (Keystone meeting on Autsim Spectrum Disorders> Section 3: Consequences A. Developmental Disorders <03.04.08> Maternal Behavior / Learning <03.11.08> Schizophrenia/Autism NOTE: associated field trip to Children’s Hospital (may not be on Tues) B. Lifelong Learning <03.18.07> Incremental learning/attention <03.25.08> no class (spring break) <04.01.08> Sleep / Environmental enrichment <04.08.08> no class (10th Neuroscience Winter Conference Austria) C. Social impact <04.15.08> Education (guest: K. Fischer, Harvard School of Education) <04.22.08> Ethics (guest: S. Hyman, Provost/HMS Neurology) <04.29.08> Public Policy (guest: J. Shonkoff, HMS Public Health) Section 4: Concluding student presentations <05.06.08> student talks I <05.06.13> student talks II

Syllabus The course is divided into three sections. First, we will cover core concepts of experience-based brain development, surveying a range of well-documented critical period effects across species. Learning objectives: introduce synaptic plasticity as a result of neuronal activity, including structural consequences of competition; concept of map formation and timing/duration of critical periods; barn owl audio-visual integration, birdsong learning, whisker barrel reorganization, orientation and ocular dominance plasticity (amblyopia), human cognitive development (concept formation, language, emotion, face recognition). Second, we will enter a detailed analysis of critical period mechanism in the visual cortex. The induction, expression and consolidation of plasticity will be explored at a cellular/molecular level. Learning objectives: traditional views of NMDA receptormediated synaptic plasticity as a model; novel insights of GABA function as a critical period trigger; homeostatic plasticity and the balance of excitation-inhibition; structural re-wiring via extracellular proteases, protein synthesis and growth factors; consolidation of structural changes by active inhibitors of neurite growth (nets, myelin) or epigenetic changes. Third, we consider the natural social implications of increased understanding and modifiability of critical period brain plasticity. From therapeutic approaches to developmental disorders to strategies for lifelong learning, as well as much broader issues such as education policy and neuroethics. Learning objectives: to challenge students to think about the global impact of experience-based brain development.

Outline of tutorial format: All meetings will consist of a 15-20 minute lecture given by myself or guest lecturer to introduce the topic, which will provide a general overview of the current research for the week’s assigned readings. Following the introductory lecture, two or three students will give a short presentation of the relevant data and help lead the discussion. The student presenters will be asked to critically evaluate the results of each paper and to discuss the relevance and impact of the key findings. The remaining students will discuss and evaluate not only the data from the assigned readings, but also the implications of these findings. You will be graded on both your participation and your oral presentations. The syllabus will be distributed the first week of class, but other readings may be substituted based upon student interest. New findings and breakthroughs that appear in the primary literature during the course will be integrated into the material when necessary. All assigned readings will be provided to you on a CD containing PDF files obtained through the Harvard library system or as photocopies. Typical weekly workload: We will read between three to six primary journal articles, reviews, or book chapters per week. One student will be responsible for presenting at least one, but no more than two, papers each week. If you do not present a paper that week, then you are responsible for providing discussion questions/topics (see below). Depending upon the class size, you should have to present about once per month. Guest speakers and field trip: This course is fortunate to welcome several guest speakers, who will greatly enhance the human relevance of the neurobiology we are learning. In the fall term Prof. Jeff Lichtman (MCB) will introduce the canonical model of synapse elimination at the neuromuscular junction. Prof. Elizabeth Spelke (Dept. Psychology) and Prof. Charles Nelson (Children’s Hospital Boston) will illustrate how higher cognitive functions emerge in human infants. In the second semester, an outside expert on epigenetic changes will present the latest findings on how early life experience can “get under the skin” and may even be transmitted across generations. A field trip to Children’s Hospital Boston will expose students to clinical presentation of developmental disorders such as autism, as an example of critical period development gone awry. Finally, the course concludes with challenging discussions about the potential to apply brain science to teaching (Dr. Kurt Fischer, Harvard School of Education), education policy (Dr. Jack Shonkoff, Director of Center on the Developing Child, Harvard School of Public Health) and the ethical implications of manipulating critical period development (Dr. Steven Hyman, Provost, Harvard Medical School). Grading: Specific basis for determining the letter grade Grade determination will be based on the following formula: Class participation – 25% Discussion questions – 20% Primary presentations – 20% Final presentation outline – 5% Final presentation – 30%

Final Letter Grades will be determined on the following scale: A: 90-100% B: 80-89% C: 70-79% D: 60-69% F: Below 60% or accumulating 4 unexcused absences Class participation will represent 25% of the final grade and will be based on the following criteria: • Providing criticisms of the models and hypotheses suggested in the readings. • Asking relevant questions that show an understanding of the material • Discussion of the implications of the work. • Attendance (2 unexcused classes will result in a drop of one letter grade, 4 unexcused absences will result in an F) The tutorial is designed to be a small, discussion-based course, which means that student attendance and participation is essential to its success. Each student will be expected to attend all class meetings and to have read all of the assigned readings to a level that will allow them to discuss the articles critically and creatively. Grades will be scored weekly on a 10-point system and the cumulative point total at the end of the year will be calculated in a manner similar to that used for the weekly presentations. Those students not presenting will be expected to discuss the implications of the work, providing criticisms of models and hypotheses, asking questions, and generally showing an understanding of that week’s topic (see discussion questions/topics). If you cannot attend a class meeting, please contact me ahead of time to ask for permission for it to be an excused absence. To be allowed to make up the work, you will need a doctor’s note or a note from the Allston Burr Senior Tutor. With my permission, you will receive credit for the week by writing a 5-page paper on a topic that we agree upon related to that week’s discussion. If you have an unexcused absence, you will not be allowed to make up the work for that week. Discussion questions and topics will constitute 20% of the final grade. You will be required to write one discussion question/topic for each reading. You are not responsible for creating discussion questions/topics for optional readings. The number of questions/ topics due each week will vary based on the number of required readings assigned for that week. You must email these questions/topics to me by 7 PM the night before the class in which they will be discussed. Possible questions/topics could point out a source of confusion in the article, offer a concern with or an alternative to the methods used, question the theoretical discussion, propose a way to extend the reported findings, or comment on a connection with one of the other readings or any other topic we have previously discussed in class. These questions are simply meant to show that you have thought about each article and to provide possible starting points for the class discussion. Because you can elaborate on your points during class discussion, your submitted questions/topics do not need to include a lot of detail. Thus, your submitted work should be concise and not longer than 4 sentences per question/topic. Quality is what matters, and short questions/topics can

easily receive full credit as long as they display creative thought. If your question/topic shows critical or creative thinking, you will receive full credit (+). If your question/topic simply regurgitates material presented in the article, you will receive half credit (check). If you do not turn in a question/topic, you will receive no credit. Primary Presentations will represent 20% of the final grade and you will be graded based on the following criteria: • Introduction of the key issue of the paper. • Explanation of the techniques employed to study that issue. • Identification and discussion of the key findings from the study. You will be responsible for and graded on presentations of the weekly readings. The size of the class will determine the frequency of oral presentations, as one student will be responsible for 1-2 papers per week. The presentations will be evaluated for clarity, organization, and comprehension. Your presentation should focus the discussion and each presentation should never last more than 15 minutes. I will be available to meet with each presenter to ensure that the article is fully understood prior to class. Each presentation will be worth 10 points. The total earned points will be added and calculated as a percentage of the total possible points. This percentage will be normalized depending upon the number of presentations. Writing an outline of the final presentation will constitute 5% of the final grade. You will be required to have chosen a topic for the final talks and have written a brief (2-4) page outline with a sample bibliography by early April. This will be discussed by individual meetings with the instructor during the month of April. The Final presentation will constitute 30% of the final grade, according to the following criteria: • Introduction to the problem (context, background, importance) • Summary of important and relevant findings • Clarity, organization, presentation, and style • Improvements made from the rough draft/student and instructor meeting • Slides will be turned in as PowerPoint file for reference. You will present a 20 minute research talk covering one of the topics discussed in the tutorial, or in consultation with me, a topic of your choice. You are encouraged to explore topics that build upon what we have discussed throughout the year, though you will explore the primary literature to a much greater degree than the assigned reading. Your talk should be addressed to the general audience, not the specialist, but may include technical data. One goal of this exercise is for you to interpret and present technical data to a general audience, similar to a Scientific American article. The final presentations will be made during the month of May and slides distributed as a handout at the beginning of class. All Harvard College policies regarding plagiarism apply.

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