Skip to main content
NCBI 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):735–744. doi: 10.1098/rstb.2002.1222

How long will long-term potentiation last?

Wickliffe C Abraham 1
PMCID: PMC1693170  PMID: 12740120

Abstract

The paramount feature of long-term potentiation (LTP) as a memory mechanism is its characteristic persistence over time. Although the basic phenomenology of LTP persistence was established 30 years ago, new insights have emerged recently about the extent of LTP persistence and its regulation by activity and experience. Thus, it is now evident that LTP, at least in the dentate gyrus, can either be decremental, lasting from hours to weeks, or stable, lasting months or longer. Although mechanisms engaged during the induction of LTP regulate its subsequent persistence, the maintenance of LTP is also governed by activity patterns post-induction, whether induced experimentally or generated by experience. These new findings establish dentate gyrus LTP as a useful model system for studying the mechanisms governing the induction, maintenance and interference with long-term memory, including very long-term memory lasting months or longer. The challenge is to study LTP persistence in other brain areas, and to relate, if possible, the properties and regulation of LTP maintenance to these same properties of the information that is actually stored in those regions.

Full Text

The Full Text of this article is available as a PDF (198.7 KB).

Selected References

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

  1. Abraham W. C., Bear M. F. Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci. 1996 Apr;19(4):126–130. doi: 10.1016/s0166-2236(96)80018-x. [DOI] [PubMed] [Google Scholar]
  2. Abraham W. C., Mason-Parker S. E., Logan B. Low-frequency stimulation does not readily cause long-term depression or depotentiation in the dentate gyrus of awake rats. Brain Res. 1996 May 25;722(1-2):217–221. doi: 10.1016/0006-8993(96)00130-8. [DOI] [PubMed] [Google Scholar]
  3. Abraham W. C., Mason-Parker S. E., Williams J., Dragunow M. Analysis of the decremental nature of LTP in the dentate gyrus. Brain Res Mol Brain Res. 1995 Jun;30(2):367–372. doi: 10.1016/0169-328x(95)00026-o. [DOI] [PubMed] [Google Scholar]
  4. Abraham W. C., Mason S. E., Demmer J., Williams J. M., Richardson C. L., Tate W. P., Lawlor P. A., Dragunow M. Correlations between immediate early gene induction and the persistence of long-term potentiation. Neuroscience. 1993 Oct;56(3):717–727. doi: 10.1016/0306-4522(93)90369-q. [DOI] [PubMed] [Google Scholar]
  5. Abraham Wickliffe C., Logan Barbara, Greenwood Jeffrey M., Dragunow Michael. Induction and experience-dependent consolidation of stable long-term potentiation lasting months in the hippocampus. J Neurosci. 2002 Nov 1;22(21):9626–9634. doi: 10.1523/JNEUROSCI.22-21-09626.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Arai A., Larson J., Lynch G. Anoxia reveals a vulnerable period in the development of long-term potentiation. Brain Res. 1990 Mar 19;511(2):353–357. doi: 10.1016/0006-8993(90)90184-d. [DOI] [PubMed] [Google Scholar]
  7. Barnes C. A., McNaughton B. L. An age comparison of the rates of acquisition and forgetting of spatial information in relation to long-term enhancement of hippocampal synapses. Behav Neurosci. 1985 Dec;99(6):1040–1048. doi: 10.1037//0735-7044.99.6.1040. [DOI] [PubMed] [Google Scholar]
  8. Barnes C. A. Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol. 1979 Feb;93(1):74–104. doi: 10.1037/h0077579. [DOI] [PubMed] [Google Scholar]
  9. Bashir Z. I., Collingridge G. L. An investigation of depotentiation of long-term potentiation in the CA1 region of the hippocampus. Exp Brain Res. 1994;100(3):437–443. doi: 10.1007/BF02738403. [DOI] [PubMed] [Google Scholar]
  10. Bliss T. V., Gardner-Medwin A. R. Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path. J Physiol. 1973 Jul;232(2):357–374. doi: 10.1113/jphysiol.1973.sp010274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Bourtchuladze R., Frenguelli B., Blendy J., Cioffi D., Schutz G., Silva A. J. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell. 1994 Oct 7;79(1):59–68. doi: 10.1016/0092-8674(94)90400-6. [DOI] [PubMed] [Google Scholar]
  13. Buzsáki G. Long-term potentiation of the commissural path-CA1 pyramidal cell synapse in the hippocampus of the freely moving rat. Neurosci Lett. 1980 Oct 2;19(3):293–296. doi: 10.1016/0304-3940(80)90276-1. [DOI] [PubMed] [Google Scholar]
  14. Chen Qi-Sheng, Wei Wei-Zheng, Shimahara Takeshi, Xie Cui-Wei. Alzheimer amyloid beta-peptide inhibits the late phase of long-term potentiation through calcineurin-dependent mechanisms in the hippocampal dentate gyrus. Neurobiol Learn Mem. 2002 May;77(3):354–371. doi: 10.1006/nlme.2001.4034. [DOI] [PubMed] [Google Scholar]
  15. Cipolotti L., Shallice T., Chan D., Fox N., Scahill R., Harrison G., Stevens J., Rudge P. Long-term retrograde amnesia...the crucial role of the hippocampus. Neuropsychologia. 2001;39(2):151–172. doi: 10.1016/s0028-3932(00)00103-2. [DOI] [PubMed] [Google Scholar]
  16. Clark Robert E., Broadbent Nicola J., Zola Stuart M., Squire Larry R. Anterograde amnesia and temporally graded retrograde amnesia for a nonspatial memory task after lesions of hippocampus and subiculum. J Neurosci. 2002 Jun 1;22(11):4663–4669. doi: 10.1523/JNEUROSCI.22-11-04663.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Davis S., Vanhoutte P., Pages C., Caboche J., Laroche S. The MAPK/ERK cascade targets both Elk-1 and cAMP response element-binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo. J Neurosci. 2000 Jun 15;20(12):4563–4572. doi: 10.1523/JNEUROSCI.20-12-04563.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Doyère V., Errington M. L., Laroche S., Bliss T. V. Low-frequency trains of paired stimuli induce long-term depression in area CA1 but not in dentate gyrus of the intact rat. Hippocampus. 1996;6(1):52–57. doi: 10.1002/(SICI)1098-1063(1996)6:1<52::AID-HIPO9>3.0.CO;2-9. [DOI] [PubMed] [Google Scholar]
  19. Doyère V., Srebro B., Laroche S. Heterosynaptic LTD and depotentiation in the medial perforant path of the dentate gyrus in the freely moving rat. J Neurophysiol. 1997 Feb;77(2):571–578. doi: 10.1152/jn.1997.77.2.571. [DOI] [PubMed] [Google Scholar]
  20. Errington M. L., Bliss T. V., Richter-Levin G., Yenk K., Doyère V., Laroche S. Stimulation at 1-5 Hz does not produce long-term depression or depotentiation in the hippocampus of the adult rat in vivo. J Neurophysiol. 1995 Oct;74(4):1793–1799. doi: 10.1152/jn.1995.74.4.1793. [DOI] [PubMed] [Google Scholar]
  21. Frey S., Bergado-Rosado J., Seidenbecher T., Pape H. C., Frey J. U. Reinforcement of early long-term potentiation (early-LTP) in dentate gyrus by stimulation of the basolateral amygdala: heterosynaptic induction mechanisms of late-LTP. J Neurosci. 2001 May 15;21(10):3697–3703. doi: 10.1523/JNEUROSCI.21-10-03697.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Frey U., Schroeder H., Matthies H. Dopaminergic antagonists prevent long-term maintenance of posttetanic LTP in the CA1 region of rat hippocampal slices. Brain Res. 1990 Jul 2;522(1):69–75. doi: 10.1016/0006-8993(90)91578-5. [DOI] [PubMed] [Google Scholar]
  24. Frégnac Y., Shulz D., Thorpe S., Bienenstock E. A cellular analogue of visual cortical plasticity. Nature. 1988 May 26;333(6171):367–370. doi: 10.1038/333367a0. [DOI] [PubMed] [Google Scholar]
  25. Fujii S., Saito K., Miyakawa H., Ito K., Kato H. Reversal of long-term potentiation (depotentiation) induced by tetanus stimulation of the input to CA1 neurons of guinea pig hippocampal slices. Brain Res. 1991 Jul 26;555(1):112–122. doi: 10.1016/0006-8993(91)90867-u. [DOI] [PubMed] [Google Scholar]
  26. Gould E., Beylin A., Tanapat P., Reeves A., Shors T. J. Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci. 1999 Mar;2(3):260–265. doi: 10.1038/6365. [DOI] [PubMed] [Google Scholar]
  27. Granger R., Wiebe S. P., Taketani M., Lynch G. Distinct memory circuits composing the hippocampal region. Hippocampus. 1996;6(6):567–578. doi: 10.1002/(SICI)1098-1063(1996)6:6<567::AID-HIPO2>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  28. Grover L. M., Teyler T. J. Different mechanisms may be required for maintenance of NMDA receptor-dependent and independent forms of long-term potentiation. Synapse. 1995 Feb;19(2):121–133. doi: 10.1002/syn.890190208. [DOI] [PubMed] [Google Scholar]
  29. Grover L. M., Teyler T. J. Two components of long-term potentiation induced by different patterns of afferent activation. Nature. 1990 Oct 4;347(6292):477–479. doi: 10.1038/347477a0. [DOI] [PubMed] [Google Scholar]
  30. Gustafsson B., Asztely F., Hanse E., Wigström H. Onset Characteristics of Long-Term Potentiation in the Guinea-Pig Hippocampal CA1 Region in Vitro. Eur J Neurosci. 1989 Jul;1(4):382–394. doi: 10.1111/j.1460-9568.1989.tb00803.x. [DOI] [PubMed] [Google Scholar]
  31. Hagiwara M., Alberts A., Brindle P., Meinkoth J., Feramisco J., Deng T., Karin M., Shenolikar S., Montminy M. Transcriptional attenuation following cAMP induction requires PP-1-mediated dephosphorylation of CREB. Cell. 1992 Jul 10;70(1):105–113. doi: 10.1016/0092-8674(92)90537-m. [DOI] [PubMed] [Google Scholar]
  32. Huang C. C., Liang Y. C., Hsu K. S. A role for extracellular adenosine in time-dependent reversal of long-term potentiation by low-frequency stimulation at hippocampal CA1 synapses. J Neurosci. 1999 Nov 15;19(22):9728–9738. doi: 10.1523/JNEUROSCI.19-22-09728.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Huang Y. Y., Kandel E. R. D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2446–2450. doi: 10.1073/pnas.92.7.2446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Huang Y. Y., Kandel E. R. Recruitment of long-lasting and protein kinase A-dependent long-term potentiation in the CA1 region of hippocampus requires repeated tetanization. Learn Mem. 1994 May-Jun;1(1):74–82. [PubMed] [Google Scholar]
  35. Impey S., Mark M., Villacres E. C., Poser S., Chavkin C., Storm D. R. Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus. Neuron. 1996 May;16(5):973–982. doi: 10.1016/s0896-6273(00)80120-8. [DOI] [PubMed] [Google Scholar]
  36. Jeffery K. J., Abraham W. C., Dragunow M., Mason S. E. Induction of Fos-like immunoreactivity and the maintenance of long-term potentiation in the dentate gyrus of unanesthetized rats. Brain Res Mol Brain Res. 1990 Oct;8(4):267–274. doi: 10.1016/0169-328x(90)90039-g. [DOI] [PubMed] [Google Scholar]
  37. Jones M. W., Errington M. L., French P. J., Fine A., Bliss T. V., Garel S., Charnay P., Bozon B., Laroche S., Davis S. A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories. Nat Neurosci. 2001 Mar;4(3):289–296. doi: 10.1038/85138. [DOI] [PubMed] [Google Scholar]
  38. Kaplan M. S., Hinds J. W. Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science. 1977 Sep 9;197(4308):1092–1094. doi: 10.1126/science.887941. [DOI] [PubMed] [Google Scholar]
  39. Kirkwood A., Dudek S. M., Gold J. T., Aizenman C. D., Bear M. F. Common forms of synaptic plasticity in the hippocampus and neocortex in vitro. Science. 1993 Jun 4;260(5113):1518–1521. doi: 10.1126/science.8502997. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. Kulla A., Reymann K. G., Manahan-Vaughan D. Time-dependent induction of depotentiation in the dentate gyrus of freely moving rats: involvement of group 2 metabotropic glutamate receptors. Eur J Neurosci. 1999 Nov;11(11):3864–3872. doi: 10.1046/j.1460-9568.1999.00807.x. [DOI] [PubMed] [Google Scholar]
  42. Leung L. S., Shen B. Long-term potentiation at the apical and basal dendritic synapses of CA1 after local stimulation in behaving rats. J Neurophysiol. 1995 May;73(5):1938–1946. doi: 10.1152/jn.1995.73.5.1938. [DOI] [PubMed] [Google Scholar]
  43. Manahan-Vaughan D., Braunewell K. H. Novelty acquisition is associated with induction of hippocampal long-term depression. Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8739–8744. doi: 10.1073/pnas.96.15.8739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Manahan-Vaughan D., Kulla A., Frey J. U. Requirement of translation but not transcription for the maintenance of long-term depression in the CA1 region of freely moving rats. J Neurosci. 2000 Nov 15;20(22):8572–8576. doi: 10.1523/JNEUROSCI.20-22-08572.2000. [DOI] [PMC free article] [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. 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]
  48. Milner P. M. A cell assembly theory of hippocampal amnesia. Neuropsychologia. 1989;27(1):23–30. doi: 10.1016/0028-3932(89)90087-0. [DOI] [PubMed] [Google Scholar]
  49. 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]
  50. Nguyen P. V., Abel T., Kandel E. R. Requirement of a critical period of transcription for induction of a late phase of LTP. Science. 1994 Aug 19;265(5175):1104–1107. doi: 10.1126/science.8066450. [DOI] [PubMed] [Google Scholar]
  51. O'Dell T. J., Kandel E. R. Low-frequency stimulation erases LTP through an NMDA receptor-mediated activation of protein phosphatases. Learn Mem. 1994 Jul-Aug;1(2):129–139. [PubMed] [Google Scholar]
  52. Olson C. R., Freeman R. D. Profile of the sensitive period for monocular deprivation in kittens. Exp Brain Res. 1980;39(1):17–21. doi: 10.1007/BF00237065. [DOI] [PubMed] [Google Scholar]
  53. Otani S., Marshall C. J., Tate W. P., Goddard G. V., Abraham W. C. Maintenance of long-term potentiation in rat dentate gyrus requires protein synthesis but not messenger RNA synthesis immediately post-tetanization. Neuroscience. 1989;28(3):519–526. doi: 10.1016/0306-4522(89)90001-8. [DOI] [PubMed] [Google Scholar]
  54. Racine R. J., Chapman C. A., Trepel C., Teskey G. C., Milgram N. W. Post-activation potentiation in the neocortex. IV. Multiple sessions required for induction of long-term potentiation in the chronic preparation. Brain Res. 1995 Dec 8;702(1-2):87–93. doi: 10.1016/0006-8993(95)01025-0. [DOI] [PubMed] [Google Scholar]
  55. Racine R. J., Milgram N. W., Hafner S. Long-term potentiation phenomena in the rat limbic forebrain. Brain Res. 1983 Feb 7;260(2):217–231. doi: 10.1016/0006-8993(83)90676-5. [DOI] [PubMed] [Google Scholar]
  56. Raymond C. R., Thompson V. L., Tate W. P., Abraham W. C. Metabotropic glutamate receptors trigger homosynaptic protein synthesis to prolong long-term potentiation. J Neurosci. 2000 Feb 1;20(3):969–976. doi: 10.1523/JNEUROSCI.20-03-00969.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. 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]
  58. Rogan M. T., Stäubli U. V., LeDoux J. E. Fear conditioning induces associative long-term potentiation in the amygdala. Nature. 1997 Dec 11;390(6660):604–607. doi: 10.1038/37601. [DOI] [PubMed] [Google Scholar]
  59. Rolls E. T. A theory of hippocampal function in memory. Hippocampus. 1996;6(6):601–620. doi: 10.1002/(SICI)1098-1063(1996)6:6<601::AID-HIPO5>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
  60. Seidenbecher T., Reymann K. G., Balschun D. A post-tetanic time window for the reinforcement of long-term potentiation by appetitive and aversive stimuli. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1494–1499. doi: 10.1073/pnas.94.4.1494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Sharp P. E., Barnes C. A., McNaughton B. L. Effects of aging on environmental modulation of hippocampal evoked responses. Behav Neurosci. 1987 Apr;101(2):170–178. doi: 10.1037//0735-7044.101.2.170. [DOI] [PubMed] [Google Scholar]
  62. Squire L. R. Mechanisms of memory. Science. 1986 Jun 27;232(4758):1612–1619. doi: 10.1126/science.3086978. [DOI] [PubMed] [Google Scholar]
  63. Staubli U., Lynch G. Stable hippocampal long-term potentiation elicited by 'theta' pattern stimulation. Brain Res. 1987 Dec 1;435(1-2):227–234. doi: 10.1016/0006-8993(87)91605-2. [DOI] [PubMed] [Google Scholar]
  64. Stäubli U., Chun D. Factors regulating the reversibility of long-term potentiation. J Neurosci. 1996 Jan 15;16(2):853–860. doi: 10.1523/JNEUROSCI.16-02-00853.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. 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]
  66. Trepel C., Racine R. J. Long-term potentiation in the neocortex of the adult, freely moving rat. Cereb Cortex. 1998 Dec;8(8):719–729. doi: 10.1093/cercor/8.8.719. [DOI] [PubMed] [Google Scholar]
  67. 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]
  68. Viola H., Furman M., Izquierdo L. A., Alonso M., Barros D. M., de Souza M. M., Izquierdo I., Medina J. H. Phosphorylated cAMP response element-binding protein as a molecular marker of memory processing in rat hippocampus: effect of novelty. J Neurosci. 2000 Dec 1;20(23):RC112–RC112. doi: 10.1523/JNEUROSCI.20-23-j0002.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Wang S., Scott B. W., Wojtowicz J. M. Heterogenous properties of dentate granule neurons in the adult rat. J Neurobiol. 2000 Feb 5;42(2):248–257. [PubMed] [Google Scholar]
  70. Wiesel T. N. Postnatal development of the visual cortex and the influence of environment. Nature. 1982 Oct 14;299(5884):583–591. doi: 10.1038/299583a0. [DOI] [PubMed] [Google Scholar]
  71. Williams J. M., Mason-Parker S. E., Abraham W. C., Tate W. P. Biphasic changes in the levels of N-methyl-D-aspartate receptor-2 subunits correlate with the induction and persistence of long-term potentiation. Brain Res Mol Brain Res. 1998 Sep 18;60(1):21–27. doi: 10.1016/s0169-328x(98)00154-5. [DOI] [PubMed] [Google Scholar]
  72. Winder D. G., Mansuy I. M., Osman M., Moallem T. M., Kandel E. R. Genetic and pharmacological evidence for a novel, intermediate phase of long-term potentiation suppressed by calcineurin. Cell. 1998 Jan 9;92(1):25–37. doi: 10.1016/s0092-8674(00)80896-x. [DOI] [PubMed] [Google Scholar]
  73. Woo Newton H., Nguyen Peter V. "Silent" metaplasticity of the late phase of long-term potentiation requires protein phosphatases. Learn Mem. 2002 Jul-Aug;9(4):202–213. doi: 10.1101/lm.498402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Xu L., Anwyl R., Rowan M. J. Spatial exploration induces a persistent reversal of long-term potentiation in rat hippocampus. Nature. 1998 Aug 27;394(6696):891–894. doi: 10.1038/29783. [DOI] [PubMed] [Google Scholar]
  75. Young D., Lawlor P. A., Leone P., Dragunow M., During M. J. Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective. Nat Med. 1999 Apr;5(4):448–453. doi: 10.1038/7449. [DOI] [PubMed] [Google Scholar]
  76. de Jonge M., Racine R. J. The effects of repeated induction of long-term potentiation in the dentate gyrus. Brain Res. 1985 Feb 25;328(1):181–185. doi: 10.1016/0006-8993(85)91341-1. [DOI] [PubMed] [Google Scholar]
  77. van Praag H., Kempermann G., Gage F. H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci. 1999 Mar;2(3):266–270. doi: 10.1038/6368. [DOI] [PubMed] [Google Scholar]

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

RESOURCES