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Home , Concept learning, Hebbian theory, Phineas Gage

1 / 4740.03F. (Also Psych./Neuro/ 6071.03. Physiological Psychology.)

Topics in the Neurobiology of and . (September-December 2018)

Tuesday 4:30 - 6:30, LSC 4269 (Psychology) *** NOTE Change in classroom***

Richard E. Brown [email protected] 494-3647

Topics in the Neurobiology of Learning and Memory. Psychology/Neuroscience 4740.03F. (Also Psych./Neuro/ 6071.03. Physiological Psychology)

Tentative Course Outline

Class 1. Tues 4 September 2018. ROOM 4269 Psychology. Course outline and historical overview of research on the neurobiology of learning and memory.

Class 2. 11 Sept. 2018. Multiple memory systems: theory and practice. of learning and memory: , cell assemblies and phase sequences.

Class 3. 18 Sept. 2018. Neuroanatomy of memory 1: The and temporal lobe memory systems. HM and .

Class 4. 25 Sept. 2018. Neuroanatomy of memory 2. The . [Outline and Parts 1 and 2 of essay due]

Class 5. 2 Oct. 2018. Neuroanatomy of memory 3. The basal ganglia.

Class 6. 9 Oct. 2018. Neuroanatomy of memory 4. The frontal cortex and working memory.

Class 7. 16 Oct. 2018. Neurochemistry of memory 1. The cholinergic system. The cholinergic hypothesis of Alzheimer's disease.

Class 8. 23 Oct. 2018. Neurochemistry of memory 2. Glutamate, NMDA receptors. Long term potentiation as a model of learning and memory processes. [Parts 3, 4 & 5 of essay due]

Class 9. 30 Oct. 2018. Memory consolidation and reconsolidation theories.

Class 10. 6 Nov. 2018. Molecular biology approaches and gene targeting methods for studying learning and memory: Gene manipulation and intracellular signal transduction systems.

2 10-18 November is the Fall break.

Class 11. 20 Nov. 2018. Neural plasticity in adulthood: Neurogenesis, neurotrophic factors and environmental enrichment in learning and memory.

Class 12. 27 Nov.2018. The epigenetic basis of learning and memory: how epigenetic changes direct gene activation and new protein synthesis. [End of class wine and cheese party.] [Final draft of essay due]

This seminar will examine current research in the study of the neurobiology of learning and memory through presentations and discussions of journal articles. Each class will (usually) consist of one review paper and two research papers. Everyone will read the review paper and two students per class will present the research papers on each topic and direct the class in the discussion. Each student will give three presentations with grades for the best two counted (20 marks each). One mark per class will be awarded for class participation (Max = 10). The essay will be a critical enquiry into one of the topics covered in the class or another topic approved by the professor and end with a short research proposal. The essay should be based primarily on articles from recent journals such as Learning and Memory, Neurobiology of Learning and Memory, , Trends in Neuroscience, Nature Neuroscience, Cell, , etc. Possible essay/discussion questions are listed for each class.

The grades (100 marks) will be based on the best 2 of 3 presentations (40%), class participation (10%) and on one essay (50%). Class participation is an important part of the seminar and will count for 10% of the final grade. This can make a difference of one grade, so if you never participate, you do not get the 10 points.

Grades are assessed on the following scale: 80/ 85/ 90% = A-, A, A+; 55-59% = C-; 70/73/ 77 = B-, B, B+; 50-54% = D. 60/65% = C, C+ Below 50% = F.

Suggested background reading.

1. Bear, M.F., Connors, B.W. and Paradiso, M.A. 2016. Neuroscience: exploring the , 4th edition. Philadelphia: Walters Kluwer. [This is the textbook for Psych./Neuro 2470. You should be familiar with this book. Chapters 24 and 25 are on learning and memory mechanisms.]

2. Squire, L.R. and Kandel, E.R. 1999. Memory: From mind to molecules. Scientific American Library. [This is an easy to read book on the neurobiology of learning and memory.]

3. Martinez, J. and Kesner, R. (Eds.) Neurobiology of Learning and Memory. (1998). Academic Press, New York. [This has some useful chapters in it.]

4. Schwartz, B., Wasserman, E.A., & Robbins, S.J. (2001) Psychology of Learning and Behavior, 5th Edition. New York: Norton. This is the textbook for the Animal Learning course (Psych 2140) and you should be familiar with basic learning theory. 3

5. Eichenbaum, H. (2002). The of Memory: An Introduction. Oxford University Press.

6. Sweatt, J.D. (2003). Mechanisms of Memory. Elsevier/Academic Press.

Presentations (20 marks): The purpose of the presentations is to describe the results of a research paper. What did the research do? Why was it done and how did it influence the field? I would expect a short introduction to the research done, a description of the experimental design, methods and results and a discussion of the meaning of the results and a critique of the results. It may be necessary to use textbooks or other papers to explain some of the and methods used. The presentation should be 40 minutes.

F Student does not give a presentation. (0 marks) D A presentation which indicates that the student has not done adequate preparation. (10-11 marks) C A presentation that covers the bare minimum and/or does not have suitable overheads. (12 marks) C+ A presentation which describes the research but has some gaps in understanding and/or poor use of overheads. (13 marks) B- A presentation that describes the paper with acceptable overheads. (14 Marks) B A good well-animated presentation which covers the research with carefully selected overheads. (15 marks) B+ Supplements the basic description with extra background material, extra questions or overheads and develops own ideas. (16 marks) A- Describes the research and develops some of the problems associated with the research. Animated presentations, not read, a good introduction and summary. (17 marks) A Delves into the problem being presented. (18 marks) A+ Adds own material above and beyond the research paper, ties the research to other issues and gives a performance which grabs our attention. (19-20 marks)

Essay: (50 marks) (1 mark per day deducted from late papers) F No paper submitted. Paper written so poorly that I am annoyed beyond belief. (0-24 marks) D Minimal effort. Uses only a textbook as a reference. Little effort to give a complete answer. Answer contains errors. (25-27 marks) C Covers bare essentials. Uses only textbooks. Answer not up-to-date. Lacks adequate figures and tables. (28- 30 marks) C+ Textbook answer. Does not integrate figures, tables and text. Reads like a list of facts. (31-33 marks) B- Good textbook answer. Covers the question and shows that you understand the material. Uses extra references. (34-35 marks) B Good textbook answer- with additional integration of tables & figures. (36-37 marks) B+ Good textbook answer- with additional integration of tables, figures, and new references. (38-39 marks) A- Adds extra material. Gives your own opinion. Goes beyond a textbook answer to ask new questions. Uses figures and drawings (40-43 marks) A Well integrated up-to-date answer which points out problems or confusion or contradiction in the standard textbook answer. (44-47 marks) A+ Up-to-date answer which develops question in a new and insightful way, integrating material from other disciplines to shed new light on the question. Develops your own theory. (48-50 marks) 4 ______Suggested outline of essay

Title page: title, author etc. Abstract 1. What is the question you want to answer? Why is it important? 2. What is the history of this question? Who first proposed it? 3. What is the theory behind this question? 4. What is the key paper/theory in this research? What did they find? What methods did they use? 5. What are the criticisms of this paper/theory? What methods were used to produce these criticisms? 6. Is there a controversy? Does person A answer the question one way and person B answer it another way? 7. Is there both animal and human research on this question? Species differences (rat vs mouse vs monkey)? 8. What do you think is the answer? Why? What is the evidence? 9. Research Proposal: What experiments would you do to show (1) that your ideas are correct and (2) to further the research on this question? 10. Summary and conclusions. 11. References. 12. Tables and Figures (Can also be embedded in the text). ______

Some examples of essay topics: Any of the seminar topics plus:

1. What is the role of the amygdala in learning? 2. What is the role of the hippocampus in learning? 3. What is the neurobiological evidence for multiple memory theory? 4. What neural networks underlie learning? 5. What is the neural basis of learning in honey bees? 6. How do cholinergic drugs influence learning and memory? 7. What is the neural basis of cognitive decline in Alzheimer's Disease? 8. What is the role of GAP43 in learning and memory? 9. What genes influence learning and memory? 10. What is the best biochemical theory of memory formation? 11. Can the same neurobiological mechanism account for short-term and long-term memory? 12. How does estrogen influence learning and memory? 13. Does learning in the endocrine and immune systems follow the same rules as learning in the CNS? 14. Why do Hebb's theories continue to influence the neurobiology of learning and memory? 15. Discuss the neurobiology of learning and memory in fish. 16. Discuss Kandel's theory of the molecular biology of learning. 17. What is the genetic theory of learning and memory? 18. Develop a neurobiological model of one type of learning (fear learning, reward learning, Pavlovian conditioning, etc). 19. What is the involvement of the in learning and memory? 20. What drugs enhance/inhibit learning and memory? ______

5 Tips on writing a paper.

Many students spend hours working on an assignment and then get a low grade because they can not write a good paper. Well written papers get good grades and it is not difficult to write one. All you need is persistence and a willingness to follow a few rules. Seven rules are:

1. Your report must answer the question. This is not as silly as it sounds. Many papers fail to answer the question posed. The question is "How does X influence learning and memory?" Use the suggested outline to answer this question. A good paper summarizes each point and then gives a summary.

2. Your report must be founded on data. To put it simply, you must know what you are talking about. You must be able to support every statement by showing the facts you used. You must cite all of the work you reference in the text (eg., the sky is blue (Smith, 1987)) and put the full reference citation (author, year, title, journal or book, volume, pages, APA style) in the reference list at the end of the paper. (Use the American Psychological Association, Publication Manual, 4th edition, 1994)

3. Your report should be about 20 pages long (5000 words). Use 1.5 or 2 line spacing.

4. Write proper English. Spelling and grammar count. Check your spelling and typing. Pay attention to word usage, sentence structure and punctuation. Omit needless words. Delete unnecessary adjectives and adverbs. Don't write "We must examine carefully...", just say "We must examine...". Ensure that your sentences are not too long. Do not write unnecessarily complex sentences. Remember that "What causal instigators do you envision giving rise to such above-mentioned consequences?" simply means "Why do you think it will happen?". Use a dictionary. Buy a copy of W. Strunk, Jr. and E.B. White The elements of style. (71 pages) and use it.

5. Make the paper interesting to read. Tell a story; don't give me a grocery list of facts. Use varied sentence structure. Don't be boring and repetitious.

6. Your report must have figures and/or tables. A figure may be a diagram, graph, line drawing, photograph, or chart. A table is a series of columns of numbers. There are two purposes of using figures and tables in your paper: to reinforce your message and to explain a particular point that you wish to make. Apparatus is more easily described in a figure than in words, as are trends in data, brain structures, and interactions. Flow charts and comparisons/contrasts can also be put into tables. Figures and tables are not merely something to be stapled to the back of your report. They are an integral part of the whole and must be referred to in the text. You might find it easier to make your figures and tables first and write your paper after. It is easy to write a lot about something you do not understand but it is difficult to draw figures or tables without understanding your subject. Your task is to communicate information concisely and accurately. The use of graphs, figures and tables can show the apparatus, methods, data and conclusions more rapidly than pages of explanation.

7. Rewrite it. Do not hand me a first draft. Write your paper, then ask a friend to read it with a red pen in their hand, to correct any errors and point out poor writing. Then rewrite it. Then read it yourself and see if you can understand it. Then rewrite it. Then give me the third draft. There will be two opportunities to hand in partial papers for my comments.

8. Research Proposal. End with an idea for future research and suggest an experiment to test your idea.

6 Historical overview of Research on the Neurobiology of Learning and Memory. NOTE: ALL READINGS CAN BE DOWNLOADED USING PUBMED. Readings for each class

Class 1. Course outline and historical overview of research on the neurobiology of learning and memory.

* Aggleton JP and Morris RGM. 2018. Memory: Looking back and looking forward. Brain and Neuroscience Advances, 2: 1–9. DOI: 10.1177/2398212818794830

*Milner, B., Squire, L., & Kandel, E.R. 1998. Cognitive neuroscience and the study of memory. Neuron, 20, 445-468.

Spatz, H.C. 1996. Hebb's of and neuronal cell assemblies. Behavioral Brain Research, 78, 3-7.

Brown, R.E. & Milner, P. 2003 The legacy of Donald O. Hebb: more than the Hebb . Nature Reviews Neuroscience, 4, 1013-1019.

Smalheiser NR, Manev H, & Costa E. 2001. RNAi and brain function: was McConnell on the right track? Trends in Neuroscience, 24, 216-218.

Cahill L, McGaugh JL, & Weinberger NM. 2001. The neurobiology of learning and memory: some reminders to remember. Trends in Neuroscience, 24, 578-581.

Some recent issues to consider in understanding the Neurobiology of Learning and Memory. [Modern history] These will be considered throughout the course.

Gallistel, CR & Matzel. 2013. The neuroscience of learning: Beyond the Hebbian synapse. Annual Review of Psychology, 64, 169-200.

Gallistel CR & Balsam PD. 2014. Time to rethink the neural mechanisms of learning and memory. Neurobiology of Learning and Memory, 108, 136-44. Poo MM, Pignatelli M, Ryan TJ, Tonegawa S, Bonhoeffer T, Martin KC, Rudenko A, Tsai LH, Tsien RW, Fishell G, Mullins C, Gonçalves JT, Shtrahman M, Johnston ST, Gage FH, Dan Y, Long J, Buzsáki G, Stevens C. 2016. What is memory? The present state of the engram. BMC Biology, 2016 May 19;14:40. doi: 10.1186/s12915-016-0261-6. I want to discuss this paper. Trettenbrein PC. 2016. The demise of the synapse as the locus of memory: A looming paradigm shift? Frontiers in Systems Neuroscience. 2016 Nov 17;10:88. and these papers. Lisman J, Cooper K, Sehgal M, Silva AJ. 2018. Memory formation depends on both synapse-specific modifications of synaptic strength and cell-specific increases in excitability. Nat Neurosci. 21(3):309- 314. doi: 10.1038/s41593-018-0076-6. Titley HK, Brunel N, Hansel C. 2017. Toward a Neurocentric View of Learning. Neuron. 95(1): 19-32. doi: 10.1016/j.neuron.2017.05.021. 7

Presenter: Richard Brown.

Other papers on the history of the neurobiology of learning and memory.

Crinella, F.M.1993. Thompson, Lashley, and Spearman: Three views of the biological basis of . Annals of the New York Academy of Sciences, 702, 159-181.

Finger, S. 1994. Origins of Neuroscience: A history of explorations into brain function. New York: Oxford University Press. [Chapter 21: Intellect and the brain, pp. 299-315. Chapter 22: The frontal lobes and intellect, pp. 316-331. Chapter 23: The nature of the memory trace, pp. 332-348. Chapter 24. The neuropathology of memory. pp. 349-368.]

Kandel, E.R. and Pittenger, C. 1999. The past, the future and the biology of memory . Philosophical Transactions of the Royal Society of London, series B, 354, 2027-2052.

Rosenzweig, M. R. 1998. Historical perspectives on the development of the biology of learning and memory. In: J. Martinez and R. Kesner (Eds.) Neurobiology of learning and memory, pp. 1-53. Academic Press, New York.

Phineas Gage.

Haas, L.F. 2001. Phineas Gage and the science of brain localization. J. Neurol. Neurosurg. Psychiatry, 71 (6), page 761.

Damasio H, Grabowski T, Frank R, Galaburda AM, Damasio AR. 1994. The return of Phineas Gage: clues about the brain from the skull of a famous patient Science 264(5162):1102-5. [Erratum in: Science 1994 Aug 26;265(5176):1159.]

Books on the neurobiology of learning and memory

Dudai, Y. 1989. The neurobiology of memory. Oxford University Press.

John,E.R. 1967. Mechanisms of memory. New York: Academic Press [BF371/J6]

Macphail, E. M. 1993. The neuroscience of animal intelligence. New York: Columbia University Press. [QP406/M3/1993].

Squire, L.R. and Schachter, D.L. 2002. of Memory, 3rd edition. New York: Guildford Press. [QP406/N535/2002]

Karl Lashley: In search of the engram.

Lashley, K.S. 1950. In search of the engram. Symposia of the Society for Experimental Biology, 4, 444- 482.

Beach, F. A. 1961. A biographical memoir [of ]. Biographical Memoirs of the National Academy of Sciences 35:162-204. 8

Beach, F. A., D. D. Hebb, C. T. Morgan, and H. W. Nissen, Eds. 1960. The Neuropsychology of Lashley. New York: McGraw-Hill.

Bruce, D. 2000. Constructing scientific psychology: Karl Lashley's mind-brain debates. ISIS 91, 824- 825.

Hebb, D. O. 1959. Karl Spencer Lashley, 1890-1958. The American Journal of Psychology 72:142-150.

Swain RA, Thompson RF. 1993. In search of engrams. Ann N Y Acad Sci. 702:27-39

Thompson, R. F. & Krupa, D. J. 1994. Organization of memory traces in the mammalian brain. Annual Review of Neuroscience, 17, 519-549.

Hebbian mechanisms of memory formation.

Hebb, D.O. 1949. The Organization of Behavior. Chapter 4. The first stage of : Growth of the assembly. (pages 60-78). New York: Wiley.

Seung, H. S. 2000. Half a century of Hebb. Nat Neurosci. 3 Suppl:1166.

Nicolelis, M.A., Fanselow, E.E., & Ghazanfar, A.A. 1997. Hebb's dream: the resurgence of cell assemblies. Neuron 19, 219-221.

Kossel, A., Bonhoeffer, T., & Bolz J. 1990. Non-Hebbian synapses in rat visual cortex. Neuroreport 1, 115-118.

Kudrimoti, H.S., Barnes, C.A., McNaughton, B.L. 1999. Reactivation of hippocampal cell assemblies: effects of behavioral state, experience, and EEG dynamics. Journal of Neuroscience, 19, 4090-101.

Milner, P.M. 1993. The mind and Donald O. Hebb. Scientific American, January, 268(1):124-129.

Sejnowski, T. J. 1999. The book of Hebb. Neuron 24, 773-776.

Stent, G.S. 1973. A physiological mechanism for Hebb's postulate of learning. Proc Natl Acad Sci U S A. 70, 997-1001.

Tsien, J. Z. 2000. Linking Hebb's coincidence-detection to memory formation. Current Opinion in Neurobiology, 10, 266-273.

Papers on planarian learning and biochemistry.

Block, R.A. & McConnell J.V. 1967. Classically conditioned discrimination in the the Planarian, Dugesia dorotocephala. Nature, 215, 1465-6.

Corning, W.C. & Ratner, S.C. 1967. Chemistry of Learing: invertebrate research. New York, Plenum Press.. [Proceedings of a symposium, sponsored by the American Institute of Biological Sciences, held at Michigan State University, September 7-10, 1966] 9

Corning W.C. & Freed S. 1968. Planarian behaviour and biochemistry. Nature, 219:1227-1229.

Dogmak, G.F.1972. Memory Molecules. Current Topics in Cell Regulation, 5, 77-97.

Jacobson, A.L., Fried, C.& Horowitz, S.D.1966. Planarians and Memory. Nature, 209, 599-601.

Jacobson, A.L., Horowitz, S.D. & Fried, C. 1967. , pseudo-conditioning, or sensitization in the Planarian. Journal of Comparative Physiology and Psychology, 1, 73-9.

McConnell, J.V. 1967. A Manual of Psychological Experimentation on Planarains. The Worm Runners Digest, Second Edition.

Ancient history of the study of memory.

Burnham, W.H. 1889. Memory, historically and experimentally considered, Part IV. Recent Theories. The American Journal of Psychology, 2 (4) (Aug., 1889), pages 568-622.

Le Goff, J. 1992. History and memory. New York: Columbia University Press. Originally published in French in 1977. [D16.9/L413/1992]

Sorabji, R. 1972. Aristotle on memory. Providence, R.I.: Brown University Press.

Yates, F. A. 1966. The art of memory. London: Routledge and Kegan Paul. [BF381/Y3]

Evolution of Learning.

Moore B. R. 2004. The evolution of learning. Biological Reviews of the Cambridge Philosophical Society.79:301-335.

Class 1. Historical overview. Essay Topics.

1. Was important in the historical development of the neurobiology of learning and memory?

2. Why is the work of Broca and Wernicke important for the study of the neurobiology of learning and memory?

3. Why is the study of neural development linked with the study of the neurobiology of learning and memory?

4. Why are Penfield, Hebb and Milner (a) linked together and (b) important for the study of the neurobiology of learning and memory?

5. What did the work of W.C. Corning, S. Freed, and J.V. McConnell contribute to the study of the neurobiology of learning and memory, and why are they absent from the history of the subject?

6. What is an engram, how did Lashley hope to find it, and what is the state of the engram today? 10

7. What were Lashley's most important contributions to the study of the neurobiology of learning and memory and what effect did the work of Lashley have on the study of the neurobiology of learning and memory?

8. What is a Hebb synapse? What is a Hebb cell assembly? Do Hebb synapses and cell assemblies explain all types of learning?

9. How can learning be compared to development?

10. Who was Tanzi and what ideas of his pre-dated Hebb's ideas?

Class 1. History Notes

1. How many types of Learning/ Memory are there? (In no particular order.)

Habituation Sensitization Classical (Pavlovian) conditioning Imitation Observational learning Latent learning Instrumental learning Trial and Error learning Operant (Skinnerian) conditioning Avoidance Learning Fear learning (Cued and contextual fear conditioning) Social learning Language learning, verbal learning Taste aversion learning (Garcia effect) Procedural learning, motor learning Spatial learning Imprinting Bird-song learning Priming Explicit vs implicit learning STM vs LTM Episodic memory Autobiographical memory Face recognition memory Object recognition memory Homing Music Declarative memory State-dependent memory Iconic memory 11

2. Classification of memory.

W. H. Thorpe (1956) Learning and in Animals. London, Methuen.

The Concepts of Learning * Habituation * Associative Learning: Conditioning; Trial and Error. * The Conditioned Reflex - Pavlovian Classical Conditioning * Instrumental (Trial and Error) Conditioning * Play * Latent Learning * Insight Learning * Imprinting * Imitation

Robert Hinde (1970) Animal Behaviour. McGraw-Hill, New York.

* Sensory Preconditioning * Perceptual Learning * Discrimination Learning * Place Learning * Song-Learning (Birds... and People) * Concept Learning * Language Learning

Bruce R. Moore (2004) The evolution of learning Biological Reviews, 79: 301-335.

A hierarchy of learning and memory

* Habituation * Sensitization * Pavlovian associative conditioning * Extinction * Discrimination learning * Garcia conditioning (taste aversion learning) * Imprinting * Observational learning * Auto-shaping * Homing and navigation * Song learning (birds) * Imitation learning * Thorndikian trial and error learning * Operant conditioning 12 * Skill learning * Tool use * Avoidance conditioning * Punishment * Language learning * Concept formation

Other types of memory. How do these relate to memory in the brain?

Memory in plants Cellular memory (liver cells remember that they are liver, not heart cells) Genomic imprinting (cells remember that they are from the mother or father) Immune system memory (the basis of vaccinations)