QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 22, 2005, 25(25):5956-5966; doi:10.1523/JNEUROSCI.0880-05.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (20) Citing Articles via Google Scholar Google Scholar Articles by Rex, C. S. Articles by Lynch, G. Search for Related Content PubMed PubMed Citation Articles by Rex, C. S. Articles by Lynch, G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Seniors' Health

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Long-Term Potentiation Is Impaired in Middle-Aged Rats: Regional Specificity and Reversal by Adenosine Receptor Antagonists

Christopher S. Rex,¹ Enikö A. Kramár,² Laura L. Colgin,² Bin Lin,² Christine M. Gall,^1,3 and Gary Lynch²

¹Department of Neurobiology and Behavior, University of California, Irvine, California 92697-4550, ²Department of Psychiatry and Human Behavior, University of California, Irvine, California 92612-1695, and ³Department of Anatomy and Neurobiology, University of California, Irvine, California 92697-1275

Memory loss in humans begins early in adult life and progresses thereafter. It is not known whether these losses reflect the failure of cellular processes that encode memory or disturbances in events that retrieve it. Here, we report that impairments in hippocampal long-term potentiation (LTP), a form of synaptic plasticity associated with memory, are present by middle age in rats but only in select portions of pyramidal cell dendritic trees. Specifically, LTP induced with theta-burst stimulation in basal dendrites of hippocampal field CA1 decayed rapidly in slices prepared from 7- to 10-month-old rats but not in slices from young adults. There were no evident age-related differences in LTP in the apical dendrites. Both the adenosine A₁ receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine and a positive AMPA receptor modulator (ampakine) offset age-related LTP deficits. Adenosine produced greater depression of synaptic responses in middle-aged versus young adult slices and in basal versus apical dendrites. These results were not associated with variations in A₁ receptor densities and may instead reflect regional and age-related differences in adenosine clearance. Pertinent to this, brief applications of A₁ receptor antagonists immediately after theta stimulation fully restored LTP in middle-aged rats. We hypothesize that the build-up of extracellular adenosine during theta activity persists into the postinduction period in the basal dendrites of middle-aged slices and thereby activates the A₁ receptor-dependent LTP reversal effect. Regardless of the underlying mechanism, the present results provide a candidate explanation for memory losses during normal aging and indicate that, with regard to plasticity, different segments of pyramidal neurons age at different rates.

Key words: LTP; basal dendrites; hippocampus; DPCPX; aging; A1 adenosine receptor; theta-burst stimulation; reversal

---

Received Nov 23, 2004; revised April 20, 2005; accepted May 14, 2005.

This article has been cited by other articles:

				J. C. Lauterborn, C. S. Rex, E. Kramar, L. Y. Chen, V. Pandyarajan, G. Lynch, and C. M. Gall Brain-Derived Neurotrophic Factor Rescues Synaptic Plasticity in a Mouse Model of Fragile X Syndrome J. Neurosci., October 3, 2007; 27(40): 10685 - 10694. [Abstract] [Full Text] [PDF]

				L. Y. Chen, C. S. Rex, M. S. Casale, C. M. Gall, and G. Lynch Changes in Synaptic Morphology Accompany Actin Signaling during LTP J. Neurosci., May 16, 2007; 27(20): 5363 - 5372. [Abstract] [Full Text] [PDF]

				G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]

				C. S. Rex, C.-Y. Lin, E. A. Kramar, L. Y. Chen, C. M. Gall, and G. Lynch Brain-Derived Neurotrophic Factor Promotes Long-Term Potentiation-Related Cytoskeletal Changes in Adult Hippocampus J. Neurosci., March 14, 2007; 27(11): 3017 - 3029. [Abstract] [Full Text] [PDF]

				C. S. Rex, J. C. Lauterborn, C.-Y. Lin, E. A. Kramar, G. A. Rogers, C. M. Gall, and G. Lynch Restoration of Long-Term Potentiation in Middle-Aged Hippocampus After Induction of Brain-Derived Neurotrophic Factor J Neurophysiol, August 1, 2006; 96(2): 677 - 685. [Abstract] [Full Text] [PDF]

				K. L. Brunson, E. Kramar, B. Lin, Y. Chen, L. L. Colgin, T. K. Yanagihara, G. Lynch, and T. Z. Baram Mechanisms of Late-Onset Cognitive Decline after Early-Life Stress J. Neurosci., October 12, 2005; 25(41): 9328 - 9338. [Abstract] [Full Text] [PDF]

				J. Larson, R. E. Jessen, D. Kim, A.-K. S. Fine, and J. du Hoffmann Age-Dependent and Selective Impairment of Long-Term Potentiation in the Anterior Piriform Cortex of Mice Lacking the Fragile X Mental Retardation Protein J. Neurosci., October 12, 2005; 25(41): 9460 - 9469. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help