Skip to main content
PMC home page
Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2003 Apr 29;358(1432):773–786. doi: 10.1098/rstb.2002.1264

Elements of a neurobiological theory of the hippocampus: the role of activity-dependent synaptic plasticity in memory.

R G M Morris 1, E I Moser 1, G Riedel 1, S J Martin 1, J Sandin 1, M Day 1, C O'Carroll 1
PMCID: PMC1693159  PMID: 12744273

Abstract

The hypothesis that synaptic plasticity is a critical component of the neural mechanisms underlying learning and memory is now widely accepted. In this article, we begin by outlining four criteria for evaluating the 'synaptic plasticity and memory (SPM)' hypothesis. We then attempt to lay the foundations for a specific neurobiological theory of hippocampal (HPC) function in which activity-dependent synaptic plasticity, such as long-term potentiation (LTP), plays a key part in the forms of memory mediated by this brain structure. HPC memory can, like other forms of memory, be divided into four processes: encoding, storage, consolidation and retrieval. We argue that synaptic plasticity is critical for the encoding and intermediate storage of memory traces that are automatically recorded in the hippocampus. These traces decay, but are sometimes retained by a process of cellular consolidation. However, we also argue that HPC synaptic plasticity is not involved in memory retrieval, and is unlikely to be involved in systems-level consolidation that depends on HPC-neocortical interactions, although neocortical synaptic plasticity does play a part. The information that has emerged from the worldwide focus on the mechanisms of induction and expression of plasticity at individual synapses has been very valuable in functional studies. Progress towards a comprehensive understanding of memory processing will also depend on the analysis of these synaptic changes within the context of a wider range of systems-level and cellular mechanisms of neuronal transmission and plasticity.

Full Text

The Full Text of this article is available as a PDF (3.8 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aggleton J. P., Brown M. W. Episodic memory, amnesia, and the hippocampal-anterior thalamic axis. Behav Brain Sci. 1999 Jun;22(3):425–489. [PubMed] [Google Scholar]
  2. Aggleton J. P., Pearce J. M. Neural systems underlying episodic memory: insights from animal research. Philos Trans R Soc Lond B Biol Sci. 2001 Sep 29;356(1413):1467–1482. doi: 10.1098/rstb.2001.0946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Amaral D. G., Ishizuka N., Claiborne B. Neurons, numbers and the hippocampal network. Prog Brain Res. 1990;83:1–11. doi: 10.1016/s0079-6123(08)61237-6. [DOI] [PubMed] [Google Scholar]
  4. Amaral D. G., Witter M. P. The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience. 1989;31(3):571–591. doi: 10.1016/0306-4522(89)90424-7. [DOI] [PubMed] [Google Scholar]
  5. Barco Angel, Alarcon Juan M., Kandel Eric R. Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture. Cell. 2002 Mar 8;108(5):689–703. doi: 10.1016/s0092-8674(02)00657-8. [DOI] [PubMed] [Google Scholar]
  6. Belvin M. P., Yin J. C. Drosophila learning and memory: recent progress and new approaches. Bioessays. 1997 Dec;19(12):1083–1089. doi: 10.1002/bies.950191207. [DOI] [PubMed] [Google Scholar]
  7. Bliss T. V., Collingridge G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993 Jan 7;361(6407):31–39. doi: 10.1038/361031a0. [DOI] [PubMed] [Google Scholar]
  8. Bliss T. V., 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 Jul;232(2):331–356. doi: 10.1113/jphysiol.1973.sp010273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brown M. W., Aggleton J. P. Recognition memory: what are the roles of the perirhinal cortex and hippocampus? Nat Rev Neurosci. 2001 Jan;2(1):51–61. doi: 10.1038/35049064. [DOI] [PubMed] [Google Scholar]
  10. Brun V. H., Ytterbo K., Morris R. G., Moser M. B., Moser E. I. Retrograde amnesia for spatial memory induced by NMDA receptor-mediated long-term potentiation. J Neurosci. 2001 Jan 1;21(1):356–362. doi: 10.1523/JNEUROSCI.21-01-00356.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Brun Vegard H., Otnass Mona K., Molden Sturla, Steffenach Hill-Aina, Witter Menno P., Moser May-Britt, Moser Edvard I. Place cells and place recognition maintained by direct entorhinal-hippocampal circuitry. Science. 2002 Jun 21;296(5576):2243–2246. doi: 10.1126/science.1071089. [DOI] [PubMed] [Google Scholar]
  12. Buzsáki G. Two-stage model of memory trace formation: a role for "noisy" brain states. Neuroscience. 1989;31(3):551–570. doi: 10.1016/0306-4522(89)90423-5. [DOI] [PubMed] [Google Scholar]
  13. Clayton N. S., Dickinson A. Episodic-like memory during cache recovery by scrub jays. Nature. 1998 Sep 17;395(6699):272–274. doi: 10.1038/26216. [DOI] [PubMed] [Google Scholar]
  14. Davis H. P., Squire L. R. Protein synthesis and memory: a review. Psychol Bull. 1984 Nov;96(3):518–559. [PubMed] [Google Scholar]
  15. Day M., Morris R. G. Memory consolidation and NMDA receptors: discrepancy between genetic and pharmacological approaches. Science. 2001 Aug 3;293(5531):755–755. doi: 10.1126/science.293.5531.755a. [DOI] [PubMed] [Google Scholar]
  16. Düzel E., Vargha-Khadem F., Heinze H. J., Mishkin M. Brain activity evidence for recognition without recollection after early hippocampal damage. Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8101–8106. doi: 10.1073/pnas.131205798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Frank L. M., Brown E. N., Wilson M. Trajectory encoding in the hippocampus and entorhinal cortex. Neuron. 2000 Jul;27(1):169–178. doi: 10.1016/s0896-6273(00)00018-0. [DOI] [PubMed] [Google Scholar]
  18. Frey U., Matthies H., Reymann K. G., Matthies H. The effect of dopaminergic D1 receptor blockade during tetanization on the expression of long-term potentiation in the rat CA1 region in vitro. Neurosci Lett. 1991 Aug 5;129(1):111–114. doi: 10.1016/0304-3940(91)90732-9. [DOI] [PubMed] [Google Scholar]
  19. Frey U., Morris R. G. Synaptic tagging and long-term potentiation. Nature. 1997 Feb 6;385(6616):533–536. doi: 10.1038/385533a0. [DOI] [PubMed] [Google Scholar]
  20. Frey U., Morris R. G. Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation. Trends Neurosci. 1998 May;21(5):181–188. doi: 10.1016/s0166-2236(97)01189-2. [DOI] [PubMed] [Google Scholar]
  21. Frey U., Morris R. G. Weak before strong: dissociating synaptic tagging and plasticity-factor accounts of late-LTP. Neuropharmacology. 1998 Apr-May;37(4-5):545–552. doi: 10.1016/s0028-3908(98)00040-9. [DOI] [PubMed] [Google Scholar]
  22. Fyhn Marianne, Molden Sturla, Hollup Stig, Moser May-Britt, Moser Edvard. Hippocampal neurons responding to first-time dislocation of a target object. Neuron. 2002 Aug 1;35(3):555–566. doi: 10.1016/s0896-6273(02)00784-5. [DOI] [PubMed] [Google Scholar]
  23. Gaffan D. What is a memory system? Horel's critique revisited. Behav Brain Res. 2001 Dec 14;127(1-2):5–11. doi: 10.1016/s0166-4328(01)00360-6. [DOI] [PubMed] [Google Scholar]
  24. Goelet P., Castellucci V. F., Schacher S., Kandel E. R. The long and the short of long-term memory--a molecular framework. 1986 Jul 31-Aug 6Nature. 322(6078):419–422. doi: 10.1038/322419a0. [DOI] [PubMed] [Google Scholar]
  25. Golding N. L., Spruston N. Dendritic sodium spikes are variable triggers of axonal action potentials in hippocampal CA1 pyramidal neurons. Neuron. 1998 Nov;21(5):1189–1200. doi: 10.1016/s0896-6273(00)80635-2. [DOI] [PubMed] [Google Scholar]
  26. Golding Nace L., Staff Nathan P., Spruston Nelson. Dendritic spikes as a mechanism for cooperative long-term potentiation. Nature. 2002 Jul 18;418(6895):326–331. doi: 10.1038/nature00854. [DOI] [PubMed] [Google Scholar]
  27. Griffiths D, Dickinson A, Clayton N. Episodic memory: what can animals remember about their past? Trends Cogn Sci. 1999 Feb;3(2):74–80. doi: 10.1016/s1364-6613(98)01272-8. [DOI] [PubMed] [Google Scholar]
  28. Hill A. J. First occurrence of hippocampal spatial firing in a new environment. Exp Neurol. 1978 Nov;62(2):282–297. doi: 10.1016/0014-4886(78)90058-4. [DOI] [PubMed] [Google Scholar]
  29. Hoffman Kari L., McNaughton Bruce L. Sleep on it: cortical reorganization after-the-fact. Trends Neurosci. 2002 Jan;25(1):1–2. doi: 10.1016/s0166-2236(00)02005-1. [DOI] [PubMed] [Google Scholar]
  30. Hédou Gaël, Mansuy Isabelle M. Inducible molecular switches for the study of long-term potentiation. Philos Trans R Soc Lond B Biol Sci. 2003 Apr 29;358(1432):797–804. doi: 10.1098/rstb.2002.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Izquierdo I., Medina J. H. Correlation between the pharmacology of long-term potentiation and the pharmacology of memory. Neurobiol Learn Mem. 1995 Jan;63(1):19–32. doi: 10.1006/nlme.1995.1002. [DOI] [PubMed] [Google Scholar]
  32. Izquierdo I., Medina J. H. On brain lesions, the milkman and Sigmunda. Trends Neurosci. 1998 Oct;21(10):423–426. doi: 10.1016/s0166-2236(98)01279-x. [DOI] [PubMed] [Google Scholar]
  33. Jeffery K. J. LTP and spatial learning--where to next? Hippocampus. 1997;7(1):95–110. doi: 10.1002/(SICI)1098-1063(1997)7:1<95::AID-HIPO10>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
  34. Kandel E. R., Schwartz J. H. Molecular biology of learning: modulation of transmitter release. Science. 1982 Oct 29;218(4571):433–443. doi: 10.1126/science.6289442. [DOI] [PubMed] [Google Scholar]
  35. Kapur N. Syndromes of retrograde amnesia: a conceptual and empirical synthesis. Psychol Bull. 1999 Nov;125(6):800–825. doi: 10.1037/0033-2909.125.6.800. [DOI] [PubMed] [Google Scholar]
  36. Kentros C., Hargreaves E., Hawkins R. D., Kandel E. R., Shapiro M., Muller R. V. Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade. Science. 1998 Jun 26;280(5372):2121–2126. doi: 10.1126/science.280.5372.2121. [DOI] [PubMed] [Google Scholar]
  37. King C., Henze D. A., Leinekugel X., Buzsáki G. Hebbian modification of a hippocampal population pattern in the rat. J Physiol. 1999 Nov 15;521(Pt 1):159–167. doi: 10.1111/j.1469-7793.1999.00159.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Krug M., Lössner B., Ott T. Anisomycin blocks the late phase of long-term potentiation in the dentate gyrus of freely moving rats. Brain Res Bull. 1984 Jul;13(1):39–42. doi: 10.1016/0361-9230(84)90005-4. [DOI] [PubMed] [Google Scholar]
  39. Lever Colin, Wills Tom, Cacucci Francesca, Burgess Neil, O'Keefe John. Long-term plasticity in hippocampal place-cell representation of environmental geometry. Nature. 2002 Mar 7;416(6876):90–94. doi: 10.1038/416090a. [DOI] [PubMed] [Google Scholar]
  40. Louie K., Wilson M. A. Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep. Neuron. 2001 Jan;29(1):145–156. doi: 10.1016/s0896-6273(01)00186-6. [DOI] [PubMed] [Google Scholar]
  41. Lynch G., Baudry M. The biochemistry of memory: a new and specific hypothesis. Science. 1984 Jun 8;224(4653):1057–1063. doi: 10.1126/science.6144182. [DOI] [PubMed] [Google Scholar]
  42. Lynch G. Long-term potentiation in the Eocene. Philos Trans R Soc Lond B Biol Sci. 2003 Apr 29;358(1432):625–628. doi: 10.1098/rstb.2002.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Maguire E. A., Vargha-Khadem F., Mishkin M. The effects of bilateral hippocampal damage on fMRI regional activations and interactions during memory retrieval. Brain. 2001 Jun;124(Pt 6):1156–1170. doi: 10.1093/brain/124.6.1156. [DOI] [PubMed] [Google Scholar]
  44. Maren S., Baudry M. Properties and mechanisms of long-term synaptic plasticity in the mammalian brain: relationships to learning and memory. Neurobiol Learn Mem. 1995 Jan;63(1):1–18. doi: 10.1006/nlme.1995.1001. [DOI] [PubMed] [Google Scholar]
  45. Marr D. Simple memory: a theory for archicortex. Philos Trans R Soc Lond B Biol Sci. 1971 Jul 1;262(841):23–81. doi: 10.1098/rstb.1971.0078. [DOI] [PubMed] [Google Scholar]
  46. Martin S. J., Grimwood P. D., Morris R. G. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci. 2000;23:649–711. doi: 10.1146/annurev.neuro.23.1.649. [DOI] [PubMed] [Google Scholar]
  47. Martin S. J., Morris R. G. M. New life in an old idea: the synaptic plasticity and memory hypothesis revisited. Hippocampus. 2002;12(5):609–636. doi: 10.1002/hipo.10107. [DOI] [PubMed] [Google Scholar]
  48. McClelland J. L., McNaughton B. L., O'Reilly R. C. Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. Psychol Rev. 1995 Jul;102(3):419–457. doi: 10.1037/0033-295X.102.3.419. [DOI] [PubMed] [Google Scholar]
  49. McGaugh J. L. Memory--a century of consolidation. Science. 2000 Jan 14;287(5451):248–251. doi: 10.1126/science.287.5451.248. [DOI] [PubMed] [Google Scholar]
  50. McHugh T. J., Blum K. I., Tsien J. Z., Tonegawa S., Wilson M. A. Impaired hippocampal representation of space in CA1-specific NMDAR1 knockout mice. Cell. 1996 Dec 27;87(7):1339–1349. doi: 10.1016/s0092-8674(00)81828-0. [DOI] [PubMed] [Google Scholar]
  51. McNaughton B. L., Barnes C. A., Meltzer J., Sutherland R. J. Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge. Exp Brain Res. 1989;76(3):485–496. doi: 10.1007/BF00248904. [DOI] [PubMed] [Google Scholar]
  52. McNaughton B. L., Barnes C. A., Rao G., Baldwin J., Rasmussen M. Long-term enhancement of hippocampal synaptic transmission and the acquisition of spatial information. J Neurosci. 1986 Feb;6(2):563–571. doi: 10.1523/JNEUROSCI.06-02-00563.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Mishkin M., Suzuki W. A., Gadian D. G., Vargha-Khadem F. Hierarchical organization of cognitive memory. Philos Trans R Soc Lond B Biol Sci. 1997 Oct 29;352(1360):1461–1467. doi: 10.1098/rstb.1997.0132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Montarolo P. G., Goelet P., Castellucci V. F., Morgan J., Kandel E. R., Schacher S. A critical period for macromolecular synthesis in long-term heterosynaptic facilitation in Aplysia. Science. 1986 Dec 5;234(4781):1249–1254. doi: 10.1126/science.3775383. [DOI] [PubMed] [Google Scholar]
  55. Morris R. G., Anderson E., Lynch G. S., Baudry M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. 1986 Feb 27-Mar 5Nature. 319(6056):774–776. doi: 10.1038/319774a0. [DOI] [PubMed] [Google Scholar]
  56. Morris R. G. Episodic-like memory in animals: psychological criteria, neural mechanisms and the value of episodic-like tasks to investigate animal models of neurodegenerative disease. Philos Trans R Soc Lond B Biol Sci. 2001 Sep 29;356(1413):1453–1465. doi: 10.1098/rstb.2001.0945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Morris R. G., Frey U. Hippocampal synaptic plasticity: role in spatial learning or the automatic recording of attended experience? Philos Trans R Soc Lond B Biol Sci. 1997 Oct 29;352(1360):1489–1503. doi: 10.1098/rstb.1997.0136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Moscovitch M. Recovered consciousness: a hypothesis concerning modularity and episodic memory. J Clin Exp Neuropsychol. 1995 Apr;17(2):276–290. doi: 10.1080/01688639508405123. [DOI] [PubMed] [Google Scholar]
  59. Moser E. I., Krobert K. A., Moser M. B., Morris R. G. Impaired spatial learning after saturation of long-term potentiation. Science. 1998 Sep 25;281(5385):2038–2042. doi: 10.1126/science.281.5385.2038. [DOI] [PubMed] [Google Scholar]
  60. Nadel L., Moscovitch M. Memory consolidation, retrograde amnesia and the hippocampal complex. Curr Opin Neurobiol. 1997 Apr;7(2):217–227. doi: 10.1016/s0959-4388(97)80010-4. [DOI] [PubMed] [Google Scholar]
  61. Nakazawa Kazu, Quirk Michael C., Chitwood Raymond A., Watanabe Masahiko, Yeckel Mark F., Sun Linus D., Kato Akira, Carr Candice A., Johnston Daniel, Wilson Matthew A. Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science. 2002 May 30;297(5579):211–218. doi: 10.1126/science.1071795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. O'Keefe J., Dostrovsky J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. 1971 Nov;34(1):171–175. doi: 10.1016/0006-8993(71)90358-1. [DOI] [PubMed] [Google Scholar]
  63. O'Reilly R. C., Rudy J. W. Conjunctive representations in learning and memory: principles of cortical and hippocampal function. Psychol Rev. 2001 Apr;108(2):311–345. doi: 10.1037/0033-295x.108.2.311. [DOI] [PubMed] [Google Scholar]
  64. Packard M. G., Teather L. A. Double dissociation of hippocampal and dorsal-striatal memory systems by posttraining intracerebral injections of 2-amino-5-phosphonopentanoic acid. Behav Neurosci. 1997 Jun;111(3):543–551. doi: 10.1037//0735-7044.111.3.543. [DOI] [PubMed] [Google Scholar]
  65. Paulsen O., Moser E. I. A model of hippocampal memory encoding and retrieval: GABAergic control of synaptic plasticity. Trends Neurosci. 1998 Jul;21(7):273–278. doi: 10.1016/s0166-2236(97)01205-8. [DOI] [PubMed] [Google Scholar]
  66. Pittenger Christopher, Kandel Eric R. In search of general mechanisms for long-lasting plasticity: Aplysia and the hippocampus. Philos Trans R Soc Lond B Biol Sci. 2003 Apr 29;358(1432):757–763. doi: 10.1098/rstb.2002.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Quirk G. J., Muller R. U., Kubie J. L., Ranck J. B., Jr The positional firing properties of medial entorhinal neurons: description and comparison with hippocampal place cells. J Neurosci. 1992 May;12(5):1945–1963. doi: 10.1523/JNEUROSCI.12-05-01945.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Riedel G., Micheau J., Lam A. G., Roloff E. L., Martin S. J., Bridge H., de Hoz L., Poeschel B., McCulloch J., Morris R. G. Reversible neural inactivation reveals hippocampal participation in several memory processes. Nat Neurosci. 1999 Oct;2(10):898–905. doi: 10.1038/13202. [DOI] [PubMed] [Google Scholar]
  69. Rioult-Pedotti M. S., Friedman D., Donoghue J. P. Learning-induced LTP in neocortex. Science. 2000 Oct 20;290(5491):533–536. doi: 10.1126/science.290.5491.533. [DOI] [PubMed] [Google Scholar]
  70. Rose S. P. Glycoproteins and memory formation. Behav Brain Res. 1995 Jan 23;66(1-2):73–78. doi: 10.1016/0166-4328(94)00127-2. [DOI] [PubMed] [Google Scholar]
  71. Rotenberg A., Abel T., Hawkins R. D., Kandel E. R., Muller R. U. Parallel instabilities of long-term potentiation, place cells, and learning caused by decreased protein kinase A activity. J Neurosci. 2000 Nov 1;20(21):8096–8102. doi: 10.1523/JNEUROSCI.20-21-08096.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Rotenberg A., Mayford M., Hawkins R. D., Kandel E. R., Muller R. U. Mice expressing activated CaMKII lack low frequency LTP and do not form stable place cells in the CA1 region of the hippocampus. Cell. 1996 Dec 27;87(7):1351–1361. doi: 10.1016/s0092-8674(00)81829-2. [DOI] [PubMed] [Google Scholar]
  73. Shimizu E., Tang Y. P., Rampon C., Tsien J. Z. NMDA receptor-dependent synaptic reinforcement as a crucial process for memory consolidation. Science. 2000 Nov 10;290(5494):1170–1174. doi: 10.1126/science.290.5494.1170. [DOI] [PubMed] [Google Scholar]
  74. Silva A. J., Stevens C. F., Tonegawa S., Wang Y. Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. Science. 1992 Jul 10;257(5067):201–206. doi: 10.1126/science.1378648. [DOI] [PubMed] [Google Scholar]
  75. Squire L. R. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev. 1992 Apr;99(2):195–231. doi: 10.1037/0033-295x.99.2.195. [DOI] [PubMed] [Google Scholar]
  76. Squire L. R., Zola-Morgan S. The medial temporal lobe memory system. Science. 1991 Sep 20;253(5026):1380–1386. doi: 10.1126/science.1896849. [DOI] [PubMed] [Google Scholar]
  77. Steele R. J., Morris R. G. Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5. Hippocampus. 1999;9(2):118–136. doi: 10.1002/(SICI)1098-1063(1999)9:2<118::AID-HIPO4>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  78. Steffenach Hill-Aina, Sloviter Robert S., Moser Edvard I., Moser May-Britt. Impaired retention of spatial memory after transection of longitudinally oriented axons of hippocampal CA3 pyramidal cells. Proc Natl Acad Sci U S A. 2002 Feb 26;99(5):3194–3198. doi: 10.1073/pnas.042700999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Stevens C. F. A million dollar question: does LTP = memory? Neuron. 1998 Jan;20(1):1–2. doi: 10.1016/s0896-6273(00)80426-2. [DOI] [PubMed] [Google Scholar]
  80. Swanson-Park J. L., Coussens C. M., Mason-Parker S. E., Raymond C. R., Hargreaves E. L., Dragunow M., Cohen A. S., Abraham W. C. A double dissociation within the hippocampus of dopamine D1/D5 receptor and beta-adrenergic receptor contributions to the persistence of long-term potentiation. Neuroscience. 1999;92(2):485–497. doi: 10.1016/s0306-4522(99)00010-x. [DOI] [PubMed] [Google Scholar]
  81. Teyler T. J., DiScenna P. Long-term potentiation. Annu Rev Neurosci. 1987;10:131–161. doi: 10.1146/annurev.ne.10.030187.001023. [DOI] [PubMed] [Google Scholar]
  82. Teyler T. J., Discenna P. Long-term potentiation as a candidate mnemonic device. Brain Res. 1984 Mar;319(1):15–28. doi: 10.1016/0165-0173(84)90027-4. [DOI] [PubMed] [Google Scholar]
  83. Thompson L. T., Best P. J. Long-term stability of the place-field activity of single units recorded from the dorsal hippocampus of freely behaving rats. Brain Res. 1990 Feb 19;509(2):299–308. doi: 10.1016/0006-8993(90)90555-p. [DOI] [PubMed] [Google Scholar]
  84. Tonegawa Susumu, Nakazawa Kazu, Wilson Matthew A. Genetic neuroscience of mammalian learning and memory. Philos Trans R Soc Lond B Biol Sci. 2003 Apr 29;358(1432):787–795. doi: 10.1098/rstb.2002.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Turrigiano G. G., Leslie K. R., Desai N. S., Rutherford L. C., Nelson S. B. Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature. 1998 Feb 26;391(6670):892–896. doi: 10.1038/36103. [DOI] [PubMed] [Google Scholar]
  86. Vargha-Khadem F., Gadian D. G., Mishkin M. Dissociations in cognitive memory: the syndrome of developmental amnesia. Philos Trans R Soc Lond B Biol Sci. 2001 Sep 29;356(1413):1435–1440. doi: 10.1098/rstb.2001.0951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Vargha-Khadem F., Gadian D. G., Watkins K. E., Connelly A., Van Paesschen W., Mishkin M. Differential effects of early hippocampal pathology on episodic and semantic memory. Science. 1997 Jul 18;277(5324):376–380. doi: 10.1126/science.277.5324.376. [DOI] [PubMed] [Google Scholar]
  88. Villarreal Desiree M., Do Viet, Haddad Evelyn, Derrick Brian E. NMDA receptor antagonists sustain LTP and spatial memory: active processes mediate LTP decay. Nat Neurosci. 2002 Jan;5(1):48–52. doi: 10.1038/nn776. [DOI] [PubMed] [Google Scholar]
  89. Wigström H., Gustafsson B. Facilitated induction of hippocampal long-lasting potentiation during blockade of inhibition. Nature. 1983 Feb 17;301(5901):603–604. doi: 10.1038/301603a0. [DOI] [PubMed] [Google Scholar]
  90. Wilson M. A., McNaughton B. L. Dynamics of the hippocampal ensemble code for space. Science. 1993 Aug 20;261(5124):1055–1058. doi: 10.1126/science.8351520. [DOI] [PubMed] [Google Scholar]
  91. Wilson M. A., McNaughton B. L. Reactivation of hippocampal ensemble memories during sleep. Science. 1994 Jul 29;265(5172):676–679. doi: 10.1126/science.8036517. [DOI] [PubMed] [Google Scholar]

Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society

RESOURCES