Teaching Materials

Mechanisms of Memory

(2nd Edition)

J. David Sweatt, Ph.D.

(To request copies of Power Point slides, please contact cindi.kellam@vanderbilt.edu)

Chapter 1: Introduction – the basics of psychological learning and memory theory

Ch 1 Sweatt Lecture / Ch 1 Figs

Suggested Reading & General References

1. Baddeley A Is working memory still working? Am. Psychol. 2001. 56:849-864.

2. Eichenbaum, H. The Cognitive Neuroscience of Memory. Oxford University Press,  New York, 2002.

3. Eichenbaum H, Yonelinas AP, Ranganath C. The medial temporal lobe and recognition memory. Annu Rev Neurosci. 2007:30:123-52.

4. Gold PE. Coordination of multiple memory systems. Neurobiol Learn Mem. 2004 Nov;82(3):230-42.

5. LeDoux JE: Synaptic self : how our brains become who we are. New York: Viking; 2001.

6. McDonald RJ, Devan BD, Hong NS. Multiple memory systems: the power of interactions.  Neurobiol Learn Mem. 2004 Nov;82(3):333-46.

7. McDonald RJ, White NM. A triple dissociation of memory systems: hippocampus, amygdala, and dorsal striatum. Behav Neurosci. 1993 Feb;107(1):3-22.

8. McNaughton BL, Battaglia FP, Jensen O, Moser EI, Moser MB. Path integration and the neural basis of the ‘cognitive map’.  Nat Rev Neurosci. 2006 Aug;7(8):663-78.

9. Milner B, Squire LR, Kandel ER. Cognitive neuroscience and the study of memory.  Neuron. 1998 Mar;20(3):445-68.

10. Shiffrin RM and Atkinson RC  Storage and retrieval processes in long-term memory.  Psychological Review 1969.  76:179-193.

11. Squire LR. Memory systems of the brain: a brief history and current perspective.  Neurobiol Learn Mem. 2004 Nov;82(3):171-7.

12. Squire, L.R. and Kandel, E.R.  Memory: From Mind to Molecules (2nd Ed.).  Roberts and Company, New York, 2008.

13. Tronson NC and Taylor JR Molecular mechanisms of memory reconsolidation. Nature reviews Neuroscience.   2007  8:262-275.   

Suggested Journal Club Articles

14. Bechara A, Tranel D, Damasio H, Adolphs R, Rockland C, Damasio AR. Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans. Science. 1995 Aug 25;269(5227):1115-8.

15. Knowlton BJ, Mangels JA, Squire LR. A neostriatal habit learning system in humans.  Science. 1996 Sep 6;273(5280):1399-402.

16. Packard MG, McGaugh JL. Inactivation of hippocampus or caudate nucleus with lidocaine differentially affects expression of place and response learning.  Neurobiol Learn Mem. 1996 Jan;65(1):65-72.

For More Information – Relevant Topic Chapters from: Learning and Memory, A Comprehensive Reference 

1.02, 1.03, 1.04, 3.01, 3.02


Chapter 2: Studies of human learning and memory

Ch 2 Sweatt Lecture / Ch 2 Figs

Suggested Reading & General References

1. Burgess N, Maguire EA, O’Keefe J. The human hippocampus and spatial and episodic memory. Neuron. 2002. 35:625-41.

2. Carey, B.  H.M., an Unforgettable Amnesiac, Dies at 82.  New York Times (Obituary) Dec 4, 2008.

3. Corkin S.  What’s new with the amnesic patient H.M.?  Nat Rev Neurosci. 2002 Feb;3(2):153-60.

4. Eichenbaum, H. and Cohen, N.J. From Conditioning to Conscious Recollection. Oxford University Press,  New York, 2001.

5. Graybiel AM. The basal ganglia: learning new tricks and loving it. Curr Opin Neurobiol. 2005 15(6):638-44.

6. Hyman SE, Malenka RC, Nestler EJ.  Neural mechanisms of addiction: the role of reward-related learning and memory.  Annu Rev Neurosci. 2006;29:565-98.

7. Kreitzer AC, Malenka RC.   Striatal plasticity and basal ganglia circuit function. Neuron. 2008 Nov 26;60(4):543-54.

8. Luria A.R. The mind of a mnemonist. Cambridge, Massachussetts.  Harvard University Press (2000) .

9. Schacter, D.L. The Seven Sins of Memory: How the Mind Forgets and Remembers.  Houghton Mifflin, New York 2002.

10. Schacter DL, Slotnick SD.  The cognitive neuroscience of memory distortion.  Neuron. 2004 Sep 30;44(1):149-60.

11. Schacter DL.  The cognitive neuroscience of memory: perspectives from neuroimaging research.  Philos Trans R Soc Lond B Biol Sci. 1997 Nov 29;352(1362):1689-95.

12. Schultz W. The primate basal ganglia and the voluntary control of behaviour. J Conscious Stud 1999; 6: 31–45.

13. Thompson RF. In search of memory traces. Annu Rev Psychol. 2005;56:1-23.

14. Zola-Morgan S, Squire LR.  Neuroanatomy of memory.  Annu Rev Neurosci. 1993;16:547-63.

Suggested Journal Club Articles

15. Clark RE, Squire LR: “Classical conditioning and brain systems: the role of awareness”. Science 1998, 280:77-81.

16. Corkin S, Amaral DG, Gonzalez RG, Johnson KA, Hyman BT  H. M.’s medial temporal lobe lesion: findings from magnetic resonance imaging. J Neurosci 1997  17:3964-3979.

17. Maguire EA, Gadian DG, Johnsrude IS, Good CD, Ashburner J, Frackowiak RS, Frith CD. Navigation-related structural change in the hippocampi of taxi drivers. Proc Natl Acad Sci U S A. 2000. 97:4398-403.

18. Scoville WB, Milner B: “Loss of recent memory after bilateral hippocampal lesions. 1957”. J Neuropsychiatry Clin Neurosci 2000, 12:103-113.

For More Information – Relevant Topic Chapters from: Learning and Memory, A Comprehensive Reference

1.05, 1.13, 1.14, 1.16, 1.24, 1.36, 2.02, 2.03, 2.04, 2.11, 2.14, 2.29, 2.32, 2.34, 2.42, 2.44, 3.03, 3.04, 3.06, 3.07 3.13, 3.14, 3.15, 3.17,3.21, 3.22, 4.12


CHAPTER 3: Non-associative learning and memory

Ch 3 Sweatt Lecture / Ch 3 Figs

Suggested Reading & General References

  1. Bailey CH, Kandel ER, Si K.  The persistence of long-term memory: a molecular approach to self-sustaining changes in learning-induced synaptic growth.  Neuron. 2004 Sep 30;44(1):49-57.

2. Bhave G, Gereau RW.  Posttranslational mechanisms of peripheral sensitization.  J Neurobiol. 2004 Oct;61(1):88-106.

3. Byrne JH, Kandel ER: “Presynaptic facilitation revisited: state and time dependence”. J Neurosci 1996, 16:425-435.

4. Kandel, E.R. In Search of Memory: The Emergence of a New Science of Mind.  W. W. Norton and Co., New York, 2007

5. Kandel ER: Cellular basis of behavior : an introduction to behavioral neurobiology. San Francisco: W. H. Freeman; 1976.

6. Kandel ER: “The molecular biology of memory storage: a dialogue between genes and synapses”. Science 2001, 294:1030-1038.

7. Lisman JE: “A mechanism for memory storage insensitive to molecular turnover: a bistable autophosphorylating kinase”. Proc Natl Acad Sci U S A 1985, 82:3055-3057.

8. Roberson ED, Sweatt JD: “A biochemical blueprint for long-term memory”. Learn Mem 1999, 6:381-388.

9. Rudy J.W. Neurobiology of Learning and Memory.  Sinauer Associates, New York, 2008

Suggested Journal Club Articles

10. Carrasquillo Y, Gereau RW.  Activation of the extracellular signal-regulated kinase in the amygdala modulates pain perception.  J Neurosci. 2007 Feb 14;27(7):1543-51.

11. Miller SG, Kennedy MB: “Regulation of brain type II Ca2+/calmodulin-dependent protein kinase by autophosphorylation: a Ca2+-triggered molecular switch”. Cell 1986, 44:861-870.

12. Si K, Giustetto M, Etkin A, Hsu R, Janisiewicz AM, Miniaci MC, Kim JH, Zhu H, Kandel ER.  A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia..  Cell. 2003 Dec 26;115(7):893-904.

13. Si K, Lindquist S, Kandel ER.  A neuronal isoform of the aplysia CPEB has prion-like properties.  Cell. 2003 Dec 26;115(7):879-91.

14. Shuster MJ, Camardo JS, Siegelbaum SA, Kandel ER: “Cyclic AMP-dependent protein kinase closes the serotonin-sensitive K+ channels of Aplysia sensory neurones in cell-free membrane patches”. Nature 1985, 313:392-395.

For More Information – Relevant Topic Chapters from: Learning and Memory, A Comprehensive Reference

1.27, 1.30, 2.12, 2.32, 4.02, 4.03, 4.04, 4.05, 4.23, 4.26, 4.27, 4.33


CHAPTER 4: Rodent behavioral learning and memory models

Ch 4 Sweatt Lecture / Ch 4 Figs

Suggested Reading & General References

1  Berman DE, Dudai Y.  “Memory extinction, learning anew, and learning the new: dissociations in the molecular machinery of learning in cortex.”  Science. 2001 Mar 23;291(5512):2417-9.

2. Crawley, JN.  “What’s Wrong With My Mouse?:” Behavioral Phenotyping of Transgenic and Knockout Mice, 2nd Edition.  Wiley-Interscience, Hoboken, NJ, 2007

3. Crawley JN, Paylor R: “A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice”. Horm Behav 1997, 31:197-211.

4. Crawley JN, Belknap JK, Collins A, Crabbe JC, Frankel W, Henderson N, Hitzemann RJ, Maxson SC, Miner LL, Silva AJ, Wehner JM, Wynshaw-Boris A, Paylor R: “Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies”. Psychopharmacology (Berl) 1997, 132:107-124.

5. Grant SG, O’Dell TJ, Karl KA, Stein PL, Soriano P, Kandel ER.  “Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice.”  Science. 1992 Dec 18;258(5090):1903-10.

6. LeDoux JE.  “Emotional memory systems in the brain.”  Behav Brain Res. 1993 Dec 20;58(1-2):69-79.

7. McCormick DA, Clark GA, Lavond DG, Thompson RF.  “Initial localization of the memory trace for a basic form of learning”.  Proc Natl Acad Sci U S A. 1982 Apr;79(8):2731-5.

8. Miller CA, Marshall JF. “Molecular substrates for retrieval and reconsolidation of cocaine-associated contextual memory.”  Neuron. 2005 Sep 15;47(6):873-84.

9. Silva AJ, Paylor R, Wehner JM, Tonegawa S. “Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice.”  Science. 1992 Jul 10;257(5067):206-11.

10. Silva AJ.  “The science of research: the principles underlying the discovery of cognitive and other biological mechanisms.”  J Physiol Paris. 2007 Jul-Nov;101(4-6):203-13.

11. Whitlock JR, Heynen AJ, Shuler MG, Bear MF.  “Learning induces long-term potentiation in the hippocampus.” Science. 2006 Aug 25;313(5790):1093-7.

Suggested Journal Club Articles

12. McCormick DA, Thompson RF.  “Cerebellum: essential involvement in the classically conditioned eyelid response”.  Science. 1984 Jan 20;223(4633):296-9.

13. Morris R: “Developments of a water-maze procedure for studying spatial learning in the rat”. J Neurosci Methods 1984, 11:47-60.

14. Nader K, Schafe GE, Le Doux JE. “Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval.”  Nature. 2000 Aug 17;406(6797):722-6.

15. Shalin SC, Hernandez CM, Dougherty MK, Morrison DK, Sweatt JD.  “Kinase suppressor of Ras1 compartmentalizes hippocampal signal transduction and subserves synaptic plasticity and memory formation.”  Neuron. 2006 Jun 1;50(5):765-79.

For More Information – Relevant Topic Chapters from: Learning and Memory, A Comprehensive Reference

1.06, 1.09, 1.11, 1.18, 1.20, 1.21, 1.22, 1.23, 1.26, 3.09, 3.13, 3.18, 3.19, 3.20, 3.24, 3.25, 3.26, 3.27


CHAPTER 5: Associative learning and unlearning

Ch 5 Sweatt lecture / Ch 5 figs

Suggested Reading & General References

1  Baxter DA, Byrne JH.  “Feeding behavior of Aplysia: a model system for comparing cellular mechanisms of classical and operant conditioning.”  Learn Mem. 2006 Nov-Dec;13(6):669-80.

2. Berry J, Krause WC, Davis RL.  “Olfactory memory traces in Drosophila.”  Prog Brain Res. 2008;169:293-304.

3. Bolhuis JJ, Gahr M.  “Neural mechanisms of birdsong memory.”  Nat Rev Neurosci. 2006 May;7(5):347-57.

4. Christian KM, Thompson RF.  “Neural substrates of eyeblink conditioning: acquisition and retention.”  Learn Mem. 2003 Nov-Dec;10(6):427-55.

5. Crow T.  “Pavlovian conditioning of Hermissenda: current cellular, molecular, and circuit perspectives.” Learn Mem. 2004 May-Jun;11(3):229-38.

6. du Lac S, Raymond JL, Sejnowski TJ, Lisberger SG.  “Learning and memory in the vestibulo-ocular reflex.”  Annu Rev Neurosci. 1995;18:409-41

7. Ito M.  “The molecular organization of cerebellar long-term depression.”  Nat Rev Neurosci. 2002 Nov;3(11):896-902.

8. Ito M. “Mechanisms of motor learning in the cerebellum.”  Brain Res. 2000 Dec 15;886(1-2):237-245.

9. Kelley AE.  “Memory and addiction: shared neural circuitry and molecular mechanisms”.  Neuron. 2004 Sep 30;44(1):161-79.

10. Lang PJ, Davis M, Ohman A.  “Fear and anxiety: animal models and human cognitive psychophysiology.”  J Affect Disord. 2000 Dec;61(3):137-59.

11. LeDoux JE.  “Emotion circuits in the brain.”  Annu Rev Neurosci. 2000;23:155-84.

12. Lukowiak K, Sangha S, Scheibenstock A, Parvez K, McComb C, Rosenegger D, Varshney N, Sadamoto H.  “A molluscan model system in the search for the engram.”  J Physiol Paris. 2003 Jan;97(1):69-76.

13. Medina JF, Repa JC, Mauk MD, LeDoux JE.  “Parallels between cerebellum- and amygdala-dependent conditioning.”  Nat Rev Neurosci. 2002 Feb;3(2):122-31.

14. Menzel R.  “Searching for the memory trace in a mini-brain, the honeybee.” Learn Mem. 2001 Mar-Apr;8(2):53-62.

15. Myers KM, Davis M.  “Mechanisms of fear extinction”.  Mol Psychiatry. 2007 Feb;12(2):120-50.

16. Phelps EA, LeDoux JE.  “Contributions of the amygdala to emotion processing: from animal models to human behavior”.  Neuron. 2005 Oct 20;48(2):175-87.

17. Rodrigues SM, Schafe GE, LeDoux JE.  “Molecular mechanisms underlying emotional learning and memory in the lateral amygdala.”  Neuron. 2004 Sep 30;44(1):75-91.

Suggested Journal Club Articles

18. Krupa DJ, Thompson JK, Thompson RF.  “Localization of a memory trace in the mammalian brain.”  Science. 1993 May 14;260(5110):989-91.

19. McKernan MG, Shinnick-Gallagher P.  “Fear conditioning induces a lasting potentiation of synaptic currents in vitro.”  Nature 1997 390:607-11.

20. Rogan MT, Staubli UV, LeDoux JE: “Fear conditioning induces associative long-term potentiation in the amygdala”. Nature 1997, 390:604-607.

For More Information – Relevant Topic Chapters from: Learning and Memory, A Comprehensive Reference

1.06, 1.10, 1.17, 1.18, 1.19, 1.25, 1.28, 1,29, 1.30, 1.31, 1.36, 2.34, 3.11, 3.14, 3.15, 3.18, 3.19, 3.20, 3.21, 3.22, 3.23, 3.24, 4.06, 4.07, 4.08, 4.09, 4,10, 4.11, 4.12, 4.13, 4.40, 4.41


CHAPTER 6: Hippocampal function in cognition

Ch 6 Sweatt Lecture / Ch 6 figs

Suggested Reading & General References

  1.  Eichenbaum H, Yonelinas AP, Ranganath C. “The medial temporal lobe and recognition memory.”  Annu Rev Neurosci. 2007;30:123-52
  2. Eichenbaum H: “A cortical-hippocampal system for declarative memory”. Nat Rev Neurosci 2000, 1:41-50.
  3. Eichenbaum H, Dudchenko P, Wood E, Shapiro M, Tanila H: “The hippocampus, memory, and place cells: is it spatial memory or a memory space?” Neuron 1999, 23:209-226.
  4. Eichenbaum H, Cohen NJ: From conditioning to conscious recollection : memory systems of the brain. Upper Saddle River, NJ: Oxford University Press; 2001.
  5. Fyhn M, Molden S, Witter MP, Moser EI, Moser MB.  “Spatial representation in the entorhinal cortex.”  Science. 2004 Aug 27;305(5688):1258-64.
  6. Hafting T, Fyhn M, Molden S, Moser MB, Moser EI. “Microstructure of a spatial map in the entorhinal cortex.” Nature. 2005 Aug 11;436(7052):801-6.
  7. Leutgeb S, Leutgeb JK, Barnes CA, Moser EI, McNaughton BL, Moser MB. “Independent codes for spatial and episodic memory in hippocampal neuronal ensembles.” Science. 2005 Jul 22;309(5734):619-23.
  8. Louie K, Wilson MA: “Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep”. Neuron 2001, 29:145-156
  9. Moser EI, Kropff E, Moser MB. “Place cells, grid cells, and the brain’s spatial representation system.”  Annu Rev Neurosci. 2008;31:69-89.

Suggested Journal Club Articles

10.  Guzowski JF, McNaughton BL, Barnes CA, Worley PF: “Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles”. Nat Neurosci 1999, 2:1120-1124.

11.  O’Keefe J, Dostrovsky J: “The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat”. Brain Res 1971, 34:171-175.

12.  Wood ER, Dudchenko PA, Eichenbaum H: “The global record of memory in hippocampal neuronal activity”. Nature 1999, 397:613-616.

For More Information – Relevant Topic Chapters from: Learning and Memory, A Comprehensive Reference

1.21, 1.33, 1.35, 1.37, 3.03, 3.05, 3.06, 3.07, 4.29


CHAPTER 7: Long-term Potentiation: A Candidate Cellular Mechanism for Infromation Storage in the CNS

Ch 7 Sweatt Lecture / Ch 7 figs

Suggested Reading & General References

  1. Barrionuevo G, Brown TH: “Associative long-term potentiation in hippocampal slices”. Proc Natl Acad Sci U S A 1983, 80:7347-7351.
  2. Chittajallu R, Alford S, Collingridge GL: “Ca2+ and synaptic plasticity”. Cell Calcium 1998, 24:377-385.
  3. Grover LM, Teyler TJ: “Two components of long-term potentiation induced by different patterns of afferent activation”. Nature 1990, 347:477-479.
  4. Harris EW, Cotman CW: “Long-term potentiation of guinea pig mossy fiber responses is not blocked by N-methyl D-aspartate antagonists”. Neurosci Lett 1986, 70:132-137.
  5. Johnston D, Amaral DG: “Hippocampus”. In: The synaptic organization of the brain Edited by Shepherd GM, 4th ed. pp. 417-458. New York: Oxford University Press; 1998: 417-458.
  6. Johnston D, Hoffman DA, Colbert CM, Magee JC: “Regulation of back-propagating action potentials in hippocampal neurons”. Curr Opin Neurobiol 1999, 9:288-292.
  7. Johnston D, Wu SM-s: Foundations of cellular neurophysiology. Cambridge, Mass.: MIT Press 1995.
  8. Linden DJ: “The return of the spike: postsynaptic action potentials and the induction of LTP and LTD”. Neuron 1999, 22:661-666.
  9. Lynch G, Larson J, Kelso S, Barrionuevo G, Schottler F: “Intracellular injections of EGTA block induction of hippocampal long-term potentiation”. Nature 1983, 305:719-721.
  10. Malinow R, Madison DV, Tsien RW: “Persistent protein kinase activity underlying long-term potentiation”. Nature 1988, 335:820-824.
  11. Maren S: “Long-term potentiation in the amygdala: a mechanism for emotional learning and memory”. Trends Neurosci 1999, 22:561-567.
  12. Martin SJ, Grimwood PD, Morris RG: “Synaptic plasticity and memory: an evaluation of the hypothesis”. Annu Rev Neurosci 2000, 23:649-711.
  13. Rioult-Pedotti MS, Friedman D, Donoghue JP: “Learning-induced LTP in neocortex”. Science 2000, 290:533-536.
  14. Stevens CF: “A million dollar question: does LTP = memory?” Neuron 1998, 20:1-2.
  15. Thomas MJ, Moody TD, Makhinson M, O’Dell TJ: “Activity-dependent beta-adrenergic modulation of low frequency stimulation induced LTP in the hippocampal CA1 region”. Neuron 1996, 17:475-482.
  16. Wigstrom H, Gustafsson B: “Postsynapt ic control of hippocampal long-term potentiation”. J Physiol (Paris) 1986, 81:228-236.

Suggested Journal Club Articles

17.  Bliss TV, Lomo T: “Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path”. J Physiol 1973, 232:331-356.4.

18.  Collingridge GL, Kehl SJ, McLennan H: “Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus”. J Physiol 1983, 334:33-46.

19.  Lee HK, Barbarosie M, Kameyama K, Bear MF, Huganir RL: “Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity”. Nature 2000, 405:955-959.

20.  Magee JC, Johnston D: “A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons”. Science 1997, 275:209-213.

21.  Whitlock JR, Heynen AJ, Shuler MG, Bear MF: “Learning induces long-term potentiation in the hippocampus.”  Science 2006, 313:1093-7.

For More Information – Relevant Topic Chapters from: Learning and Memory, A Comprehensive Reference

4.02, 4.17, 4.18, 4.19, 4.24, 4.30, 4.31, 4.36, 4.37, 4.38, 4.39, 4.40


CHAPTER 8: The NMDA Receptor

Ch 8 Sweatt Lecture / Ch 8 figs

Suggested Reading and General References

  1. Bannerman DM, Good MA, Butcher SP, Ramsay M, Morris RG: “Distinct components of spatial learning revealed by prior training and NMDA receptor blockade”. Nature 1995, 378:182-186.
  2. Davis S, Butcher SP, Morris RG: “The NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5) impairs spatial learning and LTP in vivo at intracerebral concentrations comparable to those that block LTP in vitro”. J Neurosci 1992, 12:21-34.
  3. Day M, Morris RG: “Memory consolidation and NMDA receptors: discrepancy between genetic and pharmacological approaches”. Science 2001, 293:755.
  4. Husi H, Grant SG: “Proteomics of the nervous system”. Trends Neurosci 2001, 24:259 266.
  5. Kentros C, Hargreaves E, Hawkins RD, Kandel ER, Shapiro M, Muller RV: “Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade”. Science 1998, 280:2121-2126.
  6. Kim JJ, Fanselow MS, DeCola JP, Landeira-Fernandez J: “Selective impairment of long-term but not short-term conditional fear by the N-methyl-D-aspartate antagonist APV”. Behav Neurosci 1992, 106:591-596.
  7. Konnerth A, Li J, McNamara JO, Seeburg PH: “Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo”. Cell 1998, 92:279-289.
  8. McHugh TJ, Blum KI, Tsien JZ, Tonegawa S, Wilson MA: “Impaired hippocampal representation of space in CA1-specific NMDAR1 knockout mice”. Cell 1996, 87:1339-1349.
  9. Nakazawa K, Quirk MC, Chitwood RA, Watanabe M, Yeckel MF, Sun LD, Kato A, Carr CA, Johnston D, Wilson MA, Tonegawa S: “Requirement for hippocampal CA3 NMDA receptors in associative memory recall”. Science 2002, 297:211-218.
  10. Roberts AC, Glanzman DL. “Learning in Aplysia: looking at synaptic plasticity from both sides.”  Trends Neurosci. 2003 Dec;26(12):662-70.
  11. Rondi-Reig L, Libbey M, Eichenbaum H, Tonegawa S: “CA1-specific N-methyl-D-aspartate receptor knockout mice are deficient in solving a nonspatial transverse patterning task”. Proc Natl Acad Sci U S A 2001, 98:3543-3548.
  12. Sheng M: “Molecular organization of the postsynaptic specialization”. Proc Natl Acad Sci U S A 2001, 98:7058-7061.
  13. Sprengel R, Suchanek B, Amico C, Brusa R, Burnashev N, Rozov A, Hvalby O, Jensen V, Paulsen O, Andersen P, Kim JJ, Thompson RF, Sun W, Webster LC, Grant SG, Eilers.
  14. Tang YP, Shimizu E, Dube GR, Rampon C, Kerchner GA, Zhuo M, Liu G, Tsien JZ: “Genetic enhancement of learning and memory in mice”. Nature 1999, 401:63-69.
  15. Tsien JZ, Huerta PT, Tonegawa S: “The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory”. Cell 1996, 87:1327-1338.

Suggested Journal Club Articles

16.  Hoffman DA, Magee JC, Colbert CM, Johnston D: “K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons”. Nature 1997, 387:869-875.

17.  Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG: “Proteomic analysis of NMDA receptor-adhesion protein signaling complexes”. Nat Neurosci 2000, 3:661-669.

18.  Mayer ML, Westbrook GL, Guthrie PB. “Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones.”  Nature. 1984 309:261-3.

19.  Morris RG: “Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D-aspartate receptor antagonist AP5”. J Neurosci 1989, 9:3040-3057.

20.  Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A: “Magnesium gates glutamate-activated channels in mouse central neurones.”  Nature. 1984, 307:462-5.

For More Information – Relevant Topic Chapters from: Learning and Memory, A Comprehensive Reference

4.10, 4.11, 4.13, 4.30, 4.32, 4.35, 4.39


CHAPTER 9: Biochemical mechanisms for information storage at the cellular level

Ch 9 Sweatt Lecture / Ch 9 figs

Suggested Reading and General References

  1. Adams JP, Sweatt JD. “Molecular psychology: roles for the ERK MAP kinase cascade in memory.”  Annu Rev Pharmacol Toxicol. 2002; 42:135-63.
  2. Dineley KT, Weeber EJ, Atkins C, Adams JP, Anderson AE, Sweatt JD: “Leitmotifs in the biochemistry of LTP induction: amplification, integration and coordination”. J Neurochem 2001, 77:961-971.
  3. Hayashi Y, Shi SH, Esteban JA, Piccini A, Poncer JC, Malinow R: “Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction”. Science 2000, 287:2262-2267.
  4. Klann E, Chen SJ, Sweatt JD: “Persistent protein kinase activation in the maintenance phase of long-term potentiation”. J Biol Chem 1991, 266:24253-24256.
  5. Lee HK, Barbarosie M, Kameyama K, Bear MF, Huganir RL: “Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity”. Nature 2000, 405:955-959.
  6. Lisman J, Schulman H, Cline H: “The molecular basis of CaMKII function in synaptic and behavioural memory”. Nat Rev Neurosci 2002, 3:175-190.
  7. Lisman JE, Zhabotinsky AM: “A model of synaptic memory: a CaMKII/PP1 switch that potentiates transmission by organizing an AMPA receptor anchoring assembly”. Neuron 2001, 31:191-201.
  8. Malenka RC, Bear MF. “LTP and LTD: an embarrassment of riches.”  Neuron. 2004; 44:5-21.
  9. Malinow R, Malenka RC. “AMPA receptor trafficking and synaptic plasticity.”  Annu Rev Neurosci. 2002;25:103-26.
  10. Malinow R, Madison DV, Tsien RW: “Persistent protein kinase activity underlying long-term potentiation”. Nature 1988, 335:820-824.
  11. Martin KC, Casadio A, Zhu H, E Y, Rose JC, Chen M, Bailey CH, Kandel ER: “Synapse-specific, long-term facilitation of aplysia sensory to motor synapses: a function for local protein synthesis in memory storage”. Cell 1997, 91:927-938.
  12. Scannevin RH, Huganir RL: “Postsynaptic organization and regulation of excitatory synapses”. Nat Rev Neurosci 2000, 1:133-141.
  13. Steward O, Schuman EM: “Protein synthesis at synaptic sites on dendrites”. Annu Rev Neurosci 2001, 24:299-325.
  14. Steward O, Worley PF: “A cellular mechanism for targeting newly synthesized mRNAs to synaptic sites on dendrites”. Proc Natl Acad Sci U S A 2001, 98:7062-7068.

Suggested Journal Club Articles

15.  Blitzer RD, Wong T, Nouranifar R, Iyengar R, Landau EM: “Postsynaptic cAMP pathway gates early LTP in hippocampal CA1 region”. Neuron 1995, 15:1403-1414.

16.  Frey U, Morris RG. “Synaptic tagging and long-term potentiation.”  Nature. 1997, 385:533-6.

17.  Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton AA, Sacktor TC. “Storage of spatial information by the maintenance mechanism of LTP.”  Science. 2006 313:1141-4.

18.  Takahashi T, Svoboda K, Malinow R. “Experience strengthening transmission by driving AMPA receptors into synapses.”  Science. 2003 299:1585-8.

For More Information – Relevant Topic Chapters from: Learning and Memory, A Comprehensive Reference

4.02, 4.11, 4.13, 4.17, 4.21, 4.22, 4.23, 4.25, 4.26, 4.29, 4.30, 4.31, 4.32, 4.33, 4.34, 4,36, 4.37, 4.38, 4.40


CHAPTER 10: Molecular genetic mechanism for long-term information storage at the cellular level

Ch 10 Sweatt Lecture / Ch 10 figs

Suggested Reading and General References

  1. Alberini CM. “Transcription factors in long-term memory and synaptic plasticity.”  Physiol Rev. 2009 89:121-45.
  2. Barco A, Alarcon JM, Kandel ER: “Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture”. Cell 2002, 108:689-703.
  3. Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva AJ: “Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein”. Cell 1994, 79:59-68.
  4. Brivanlou AH, Darnell JE, Jr.: “Signal transduction and the control of gene expression”. Science 2002, 295:813-818.
  5. Cole AJ, Saffen DW, Baraban JM, Worley PF: “Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation”. Nature 1989, 340:474-476.
  6. Eisch AJ, Cameron HA, Encinas JM, Meltzer LA, Ming GL, Overstreet-Wadiche LS. “Adult neurogenesis, mental health, and mental illness: hope or hype?”  J Neurosci. 2008 28:11785-91.
  7. Flavell SW, Greenberg ME. “Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system.”  Annu Rev Neurosci. 2008, 31:563-90.
  8. Gass P, Wolfer DP, Balschun D, Rudolph D, Frey U, Lipp HP, Schutz G: “Deficits in memory tasks of mice with CREB mutations depend on gene dosage”. Learn Mem 1998, 5:274-288.
  9. Gräff J, Mansuy IM. “Epigenetic codes in cognition and behaviour.”  Behav Brain Res. 2008 192:70-87.
  10. Greer PL, Greenberg ME. “From synapse to nucleus: calcium-dependent gene transcription in the control of synapse development and function.”  Neuron. 2008 59:846-60
  11. Guzowski JF, Lyford GL, Stevenson GD, Houston FP, McGaugh JL, Worley PF, Barnes CA: “Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory”. J Neurosci 2000, 20:3993-4001.
  12. Huang F, Chotiner JK, Steward O. “Actin polymerization and ERK phosphorylation are required for Arc/Arg3.1 mRNA targeting to activated synaptic sites on dendrites.” J Neurosci. 2007 27:9054-67.
  13. Levenson JM, Sweatt JD. “Epigenetic mechanisms in memory formation.”  Nat Rev Neurosci. 2005 6:108-18.
  14. Lubin FD, Sweatt JD.: “The IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories”. Neuron 2007 55:942-57.
  15. Nguyen PV, Abel T, Kandel ER: “Requirement of a critical period of transcription for induction of a late phase of LTP”. Science 1994, 265:1104-1107.
  16. Roberson ED, English JD, Adams JP, Selcher JC, Kondratick C, Sweatt JD: “The mitogen-activated protein kinase cascade couples PKA and PKC to cAMP response element binding protein phosphorylation in area CA1 of hippocampus”. J Neurosci 1999, 19:4337-4348.
  17. Schuman EM, Dynes JL, Steward O. “Synaptic regulation of translation of dendritic mRNAs.”  J Neurosci. 2006 26:7143-6.
  18. Weaver, I. C. et al. “Epigenetic programming by maternal behavior.” Nat Neurosci 7, 847-54 (2004)
  19. Wood MA, Hawk JD, Abel T.: “Combinatorial chromatin modifications and memory storage: a code for memory”. Learn Mem 2006 13:241-4.
  20. Zhao C, Deng W, Gage FH. “Mechanisms and functional implications of adult neurogenesis.”  Cell. 2008 132:645-60.

Suggested Journal Club Articles

21.  Atkins CM, Selcher JC, Petraitis JJ, Trzaskos JM, Sweatt JD. “The MAPK cascade is required for mammalian associative learning.”  Nat Neurosci. 1998 1:602-9.

22.  Borrelli E, Nestler EJ, Allis CD, Sassone-Corsi P. “Decoding the epigenetic language of neuronal plasticity.”  Neuron. 2008 Dec 26;60(6):961-74.

23.  Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH.: “Recovery of learning and memory is associated with chromatin remodeling.”  Nature 2007  447:178-82.

24.  Reijmers LG, Perkins BL, Matsuo N, Mayford M. “Localization of a stable neural correlate of associative memory”  Science. 2007 317:1230-3.

25.  Shema R, Sacktor TC, Dudai Y. “Rapid erasure of long-term memory associations in the cortex by an inhibitor of PKM zeta.”  Science. 2007 317:951-3.

For More Information – Relevant Topic Chapters from: Learning and Memory, A Comprehensive Reference

4.02, 4.11, 4.12, 4.13, 4.14, 4.21, 4.22, 4.25, 4.26, 4.27, 4.28, 4.29, 4.32, 4.33, 4.34, 4.35, 4.40, 4.41, 4.42


CHAPTER 11: Inherited disorders of human memory-mental retardation syndromes

Ch 11 Sweatt Lecture / Ch 11 figs

Suggested Reading and General References

  1. Abel T, Zukin RS.: “Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders”. Curr Opin Pharmacol. 2008:8:57-64.
  2. Alarcon JM, et al. : “Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration.” Neuron 2004: 947-59.
  3. Bear MF, Huber KM, Warren ST. “The mGluR theory of fragile X mental retardation.” Trends Neurosci. 2004 Jul;27(7):370-7.
  4. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY. “MeCP2, a key contributor to neurological disease, activates and represses transcription.”  Science 2008:  320:1224-1229.
  5. Costa-Mattioli M, Sossin WS, Klann E, Sonenberg N. “Translational control of long-lasting synaptic plasticity and memory.”  Neuron. 2009 61:10-26.
  6. Dolen G, Osterweil E, Rao BS, Smith GB, Auerbach BD, Chattarji S, Bear MF. “Correction of fragile X syndrome in mice.”  Neuron. 2007 56:955-62.
  7. Greer PL, Zieg J, Greenberg ME. “Activity-dependent transcription and disorders of human cognition.” Am J Psychiatry. 2009 Jan;166(1):14-5.
  8. Guy J, Gan J, Selfridge J, Cobb S, Bird A.: “Reversal of neurological defects in a mouse model of Rett syndrome.” Science 2007:  315:1143-7.
  9. Korzus E, Rosenfeld MG, Mayford M: “CBP histone acetyltransferase activity is a critical component of memory consolidation.” Neuron 2004: 961-72.
  10. Levenson JM, et al. : “Regulation of histone acetylation during memory formation in the hippocampus.”  J Biol Chem 279. 2004: 40545-59.
  11. Silva AJ, Frankland PW, Marowitz Z, Friedman E, Lazlo G, Cioffi D, Jacks T, Bourtchuladze R: “A mouse model for the learning and memory deficits associated with neurofibromatosis type I”. Nat Genet 1997, 15:281-284.
  12. Sweatt JD: “Protooncogenes subserve memory formation in the adult CNS”. Neuron 2001, 31:671-674.
  13. Vaillend C, Poirier R, Laroche S. “Genes, plasticity and mental retardation.” Behav Brain Res. 2008 192:88-105.
  14. Weeber EJ, Sweatt JD: “Molecular neurobiology of human cognition”. Neuron 2002, 33:845-848.
  15. Vaillend C, Poirier R, Laroche S. “Genes, plasticity and mental retardation.”  Behav Brain Res. 2008 192:88-105.

Suggested Journal Club Articles

16.  Amir RE, et al. : “Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl- CpG-binding protein 2.” Nat Genet 1999  23: 185-8.

17.  Jiang YH, Armstrong D, Albrecht U, Atkins CM, Noebels JL, Eichele G, Sweatt JD, Beaudet AL: “Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation”. Neuron 1998, 21:799-811.

18.  Petrij F, et al.:  “Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP.” Nature 1995  376: 348-51.

19.  Van Woerden GM, Harris KD, Hojjati MR, Gustin RM, Qiu S, de Avila Freire R, Jiang YH, Elgersma Y, Weeber EJ. “Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of alphaCaMKII inhibitory phosphorylation.”  Nat Neurosci. 2007 10:280-2.

For More Information – Relevant Topic Chapters from: Learning and Memory, A Comprehensive Reference

2.37, 2.38, 2.39, 2.40, 2.43, 3.04, 3.05, 3.27, 4.19, 4.24, 4.25, 4.26, 4.42


CHAPTER 12: Aging-related memory disorders – Alzheimer’s Disease

 Ch 12 Sweatt Lecture / Ch 12 figs

Suggested Reading and General References

  1. Billings LM, Oddo S, Green KN, McGaugh JL, LaFerla FM. “Intraneuronal Abeta causes the onset of early Alzheimer’s disease-related cognitive deficits in transgenic mice”.  Neuron. 2005 45:675-88.
  2. Braak H, Braak E, Bohl J: “Staging of Alzheimer-related cortical destruction”. Eur Neurol 1993, 33:403-408.
  3. Burke SN, Barnes CA. “Neural plasticity in the ageing brain.” Nat Rev Neurosci. 2006 7:30-40.
  4. Chapman PF, White GL, Jones MW, Cooper-Blacketer D, Marshall VJ, Irizarry M, Younkin L, Good MA, Bliss TV, Hyman BT, Younkin SG, Hsiao KK.  “Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice”. Nat Neurosci. 1999 2:271-6.
  5. Herz J and Chen Y. “Reelin, lipoprotein receptors and synaptic plasticity.” Nat. Rev. Neurosci. 7. 2006: 850-859.
  6. Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM. “Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction.” Neuron. 2003 39:409-21.
  7. Roberson ED and Mucke L. “100 years and counting: Prospects for defeating Alzheimer’s disease.”  Science 314. 2006: 781-784.
  8. Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu GQ, Mucke L. “Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model.”  Science. 2007 316:750-4.
  9. Selkoe DJ.  “Alzheimer’s disease is a synaptic failure.” Science. 2002 298:789-91.
  10. Selkoe DJ, Wolfe MS. “Presenilin: running with scissors in the membrane.”  Cell. 2007 131:215-21.
  11. Walsh DM, Selkoe DJ. “Deciphering the molecular basis of memory failure in Alzheimer’s disease.”  Neuron. 2004 44:181-93.
  12. Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, Delon MR: “Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain”. Science 1982, 215:1237-1239.
  13. Wong PC, Cai H, Borchelt DR, Price DL.  “Genetically engineered models relevant to neurodegenerative disorders: their value for understanding disease mechanisms and designing/testing experimental therapeutics.”  J Mol Neurosci. 2001 17:233-57.
  14. Wu W, Brickman AM, Luchsinger J, Ferrazzano P, Pichiule P, Yoshita M, Brown T, DeCarli C, Barnes CA, Mayeux R, Vannucci SJ, Small SA.  “The brain in the age of old: the hippocampal formation is targeted differentially by diseases of late life.”  Ann Neurol. 2008 64:698-706.

Suggested Journal Club Articles

15.  Barnes CA, Suster MS, Shen J, McNaughton BL. “Multistability of cognitive maps in the hippocampus of old rats.”  Nature. 1997 388:272-5.

16.  Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G: “Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice”. Science 1996, 274:99-102.

17.  Klunk WE, Engler H, Nordberg A, et al. “Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B.” Ann. Neurol. 55. 2004: 306-319.

18.  Snowdon DA, Kemper SJ, Mortimer JA, Greiner LH, Wekstein DR, Markesbery WR: “Linguistic ability in early life and cognitive function and Alzheimer’s disease in late life. Findings from the Nun Study”. Jama 1996, 275:528-532.

For More Information – Relevant Topic Chapters from: Learning and Memory, A Comprehensive Reference

2.41, 3.25, 3.26, 3.27, 3.28, 3.29, 4.15