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):765–772. doi: 10.1098/rstb.2002.1244

Long-term potentiation and the ageing brain.

C A Barnes 1
PMCID: PMC1693160  PMID: 12740124

Abstract

Ageing is associated with learning and memory impairments. Data are reviewed that suggest that age-related impairments of hippocampal-dependent forms of memory, may be caused, in part, by altered synaptic plasticity mechanisms in the hippocampus, including long-term potentiation (LTP). To the extent that the mechanisms responsible for LTP can be understood, it may be possible to develop therapeutic approaches to alleviate memory decline in normal ageing.

Full Text

The Full Text of this article is available as a PDF (436.2 KB).

Selected References

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

  1. Bach M. E., Barad M., Son H., Zhuo M., Lu Y. F., Shih R., Mansuy I., Hawkins R. D., Kandel E. R. Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway. Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5280–5285. doi: 10.1073/pnas.96.9.5280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Barnes C. A., McNaughton B. L. Physiological compensation for loss of afferent synapses in rat hippocampal granule cells during senescence. J Physiol. 1980 Dec;309:473–485. doi: 10.1113/jphysiol.1980.sp013521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Barnes C. A. Normal aging: regionally specific changes in hippocampal synaptic transmission. Trends Neurosci. 1994 Jan;17(1):13–18. doi: 10.1016/0166-2236(94)90029-9. [DOI] [PubMed] [Google Scholar]
  6. Barnes C. A., Rao G., Foster T. C., McNaughton B. L. Region-specific age effects on AMPA sensitivity: electrophysiological evidence for loss of synaptic contacts in hippocampal field CA1. Hippocampus. 1992 Oct;2(4):457–468. doi: 10.1002/hipo.450020413. [DOI] [PubMed] [Google Scholar]
  7. Barnes C. A., Rao G., Houston F. P. LTP induction threshold change in old rats at the perforant path--granule cell synapse. Neurobiol Aging. 2000 Sep-Oct;21(5):613–620. doi: 10.1016/s0197-4580(00)00163-9. [DOI] [PubMed] [Google Scholar]
  8. Barnes C. A., Rao G., Orr G. Age-related decrease in the Schaffer collateral-evoked EPSP in awake, freely behaving rats. Neural Plast. 2000;7(3):167–178. doi: 10.1155/NP.2000.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Barnes C. A., Suster M. S., Shen J., McNaughton B. L. Multistability of cognitive maps in the hippocampus of old rats. Nature. 1997 Jul 17;388(6639):272–275. doi: 10.1038/40859. [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. Blum K. I., Abbott L. F. A model of spatial map formation in the hippocampus of the rat. Neural Comput. 1996 Jan;8(1):85–93. doi: 10.1162/neco.1996.8.1.85. [DOI] [PubMed] [Google Scholar]
  13. Deupree D. L., Bradley J., Turner D. A. Age-related alterations in potentiation in the CA1 region in F344 rats. Neurobiol Aging. 1993 May-Jun;14(3):249–258. doi: 10.1016/0197-4580(93)90009-z. [DOI] [PubMed] [Google Scholar]
  14. Douglas R. M., Goddard G. V. Long-term potentiation of the perforant path-granule cell synapse in the rat hippocampus. Brain Res. 1975 Mar 21;86(2):205–215. doi: 10.1016/0006-8993(75)90697-6. [DOI] [PubMed] [Google Scholar]
  15. Ekstrom A. D., Meltzer J., McNaughton B. L., Barnes C. A. NMDA receptor antagonism blocks experience-dependent expansion of hippocampal "place fields". Neuron. 2001 Aug 30;31(4):631–638. doi: 10.1016/s0896-6273(01)00401-9. [DOI] [PubMed] [Google Scholar]
  16. Foster T. C., Barnes C. A., Rao G., McNaughton B. L. Increase in perforant path quantal size in aged F-344 rats. Neurobiol Aging. 1991 Sep-Oct;12(5):441–448. doi: 10.1016/0197-4580(91)90071-q. [DOI] [PubMed] [Google Scholar]
  17. Geinisman Y., deToledo-Morrell L., Morrell F., Persina I. S., Rossi M. Age-related loss of axospinous synapses formed by two afferent systems in the rat dentate gyrus as revealed by the unbiased stereological dissector technique. Hippocampus. 1992 Oct;2(4):437–444. doi: 10.1002/hipo.450020411. [DOI] [PubMed] [Google Scholar]
  18. Gothard K. M., Skaggs W. E., McNaughton B. L. Dynamics of mismatch correction in the hippocampal ensemble code for space: interaction between path integration and environmental cues. J Neurosci. 1996 Dec 15;16(24):8027–8040. doi: 10.1523/JNEUROSCI.16-24-08027.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Kerr D. S., Campbell L. W., Applegate M. D., Brodish A., Landfield P. W. Chronic stress-induced acceleration of electrophysiologic and morphometric biomarkers of hippocampal aging. J Neurosci. 1991 May;11(5):1316–1324. doi: 10.1523/JNEUROSCI.11-05-01316.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Landfield P. W., Lynch G. Impaired monosynaptic potentiation in in vitro hippocampal slices from aged, memory-deficient rats. J Gerontol. 1977 Sep;32(5):523–533. doi: 10.1093/geronj/32.5.523. [DOI] [PubMed] [Google Scholar]
  23. Landfield P. W., McGaugh J. L., Lynch G. Impaired synaptic potentiation processes in the hippocampus of aged, memory-deficient rats. Brain Res. 1978 Jul 7;150(1):85–101. doi: 10.1016/0006-8993(78)90655-8. [DOI] [PubMed] [Google Scholar]
  24. Landfield P. W., Pitler T. A. Prolonged Ca2+-dependent afterhyperpolarizations in hippocampal neurons of aged rats. Science. 1984 Nov 30;226(4678):1089–1092. doi: 10.1126/science.6494926. [DOI] [PubMed] [Google Scholar]
  25. Levy W. B., Steward O. Temporal contiguity requirements for long-term associative potentiation/depression in the hippocampus. Neuroscience. 1983 Apr;8(4):791–797. doi: 10.1016/0306-4522(83)90010-6. [DOI] [PubMed] [Google Scholar]
  26. Markowska A. L., Stone W. S., Ingram D. K., Reynolds J., Gold P. E., Conti L. H., Pontecorvo M. J., Wenk G. L., Olton D. S. Individual differences in aging: behavioral and neurobiological correlates. Neurobiol Aging. 1989 Jan-Feb;10(1):31–43. doi: 10.1016/s0197-4580(89)80008-9. [DOI] [PubMed] [Google Scholar]
  27. Marr D. A theory for cerebral neocortex. Proc R Soc Lond B Biol Sci. 1970 Nov 3;176(1043):161–234. doi: 10.1098/rspb.1970.0040. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Mehta M. R., Barnes C. A., McNaughton B. L. Experience-dependent, asymmetric expansion of hippocampal place fields. Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8918–8921. doi: 10.1073/pnas.94.16.8918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Moore C. I., Browning M. D., Rose G. M. Hippocampal plasticity induced by primed burst, but not long-term potentiation, stimulation is impaired in area CA1 of aged Fischer 344 rats. Hippocampus. 1993 Jan;3(1):57–66. doi: 10.1002/hipo.450030106. [DOI] [PubMed] [Google Scholar]
  31. Norris C. M., Korol D. L., Foster T. C. Increased susceptibility to induction of long-term depression and long-term potentiation reversal during aging. J Neurosci. 1996 Sep 1;16(17):5382–5392. doi: 10.1523/JNEUROSCI.16-17-05382.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Oler J. A., Markus E. J. Age-related deficits in the ability to encode contextual change: a place cell analysis. Hippocampus. 2000;10(3):338–350. doi: 10.1002/1098-1063(2000)10:3<338::AID-HIPO14>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
  34. Potier B., Poindessous-Jazat F., Dutar P., Billard J. M. NMDA receptor activation in the aged rat hippocampus. Exp Gerontol. 2000 Dec;35(9-10):1185–1199. doi: 10.1016/s0531-5565(00)00122-4. [DOI] [PubMed] [Google Scholar]
  35. Rapp P. R., Gallagher M. Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9926–9930. doi: 10.1073/pnas.93.18.9926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rasmussen T., Schliemann T., Sørensen J. C., Zimmer J., West M. J. Memory impaired aged rats: no loss of principal hippocampal and subicular neurons. Neurobiol Aging. 1996 Jan-Feb;17(1):143–147. doi: 10.1016/0197-4580(95)02032-2. [DOI] [PubMed] [Google Scholar]
  37. Redish A. D., McNaughton B. L., Barnes C. A. Reconciling Barnes et al. (1997) and Tanila et al. (1997a,b). Hippocampus. 1998;8(5):438–443. doi: 10.1002/(SICI)1098-1063(1998)8:5<438::AID-HIPO4>3.0.CO;2-Z. [DOI] [PubMed] [Google Scholar]
  38. Redish A. D., Rosenzweig E. S., Bohanick J. D., McNaughton B. L., Barnes C. A. Dynamics of hippocampal ensemble activity realignment: time versus space. J Neurosci. 2000 Dec 15;20(24):9298–9309. doi: 10.1523/JNEUROSCI.20-24-09298.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Samsonovich A., McNaughton B. L. Path integration and cognitive mapping in a continuous attractor neural network model. J Neurosci. 1997 Aug 1;17(15):5900–5920. doi: 10.1523/JNEUROSCI.17-15-05900.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Shankar S., Teyler T. J., Robbins N. Aging differentially alters forms of long-term potentiation in rat hippocampal area CA1. J Neurophysiol. 1998 Jan;79(1):334–341. doi: 10.1152/jn.1998.79.1.334. [DOI] [PubMed] [Google Scholar]
  41. Shen J., Barnes C. A., McNaughton B. L., Skaggs W. E., Weaver K. L. The effect of aging on experience-dependent plasticity of hippocampal place cells. J Neurosci. 1997 Sep 1;17(17):6769–6782. doi: 10.1523/JNEUROSCI.17-17-06769.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Skaggs W. E., McNaughton B. L. Replay of neuronal firing sequences in rat hippocampus during sleep following spatial experience. Science. 1996 Mar 29;271(5257):1870–1873. doi: 10.1126/science.271.5257.1870. [DOI] [PubMed] [Google Scholar]
  43. Tanila H., Shapiro M., Gallagher M., Eichenbaum H. Brain aging: changes in the nature of information coding by the hippocampus. J Neurosci. 1997 Jul 1;17(13):5155–5166. doi: 10.1523/JNEUROSCI.17-13-05155.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Thibault O., Landfield P. W. Increase in single L-type calcium channels in hippocampal neurons during aging. Science. 1996 May 17;272(5264):1017–1020. doi: 10.1126/science.272.5264.1017. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. 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]
  47. de Toledo-Morrell L., Morrell F. Electrophysiological markers of aging and memory loss in rats. Ann N Y Acad Sci. 1985;444:296–311. doi: 10.1111/j.1749-6632.1985.tb37598.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES