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This Article Full Text Full Text (PDF) All Versions of this Article: 99/6/2760    most recent 01276.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yang, Z. Articles by Barnes, C. A. Search for Related Content PubMed PubMed Citation Articles by Yang, Z. Articles by Barnes, C. A.

Synaptic Commitment: Developmentally Regulated Reciprocal Changes in Hippocampal Granule Cell NMDA and AMPA Receptors Over the Lifespan

¹Arizona Research Laboratories Division of Neural Systems, Memory and Aging; ²Evelyn F. McKnight Brain Institute; and Departments of ³Psychology, ⁴Physiology, and ⁵Neurology, University of Arizona, Tucson, Arizona

Submitted 21 November 2007; accepted in final form 10 April 2008

Synaptic transmission in hippocampal field CA1 is largely N-methyl-D-aspartate receptor (NMDA_R) dependent during the early postnatal period. It becomes increasingly mediated by -amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) receptors until an adult ratio of AMPA to NMDA receptors is achieved. It is shown here that increases in the AMPA receptor (AMPA_R)-mediated field potential response continue over the life span of the F-344 rat at the perforant path–granule cell synapse in the dentate gyrus. In contrast, the NMDA_R-dependent component of the response decreases with age between 1 and 27 mo, leading to an increase of AMPA_R/NMDA_R ratio with age. One possible explanation of this age difference is that the AMPA_R/NMDA_R ratio can be modified by experience. To test the idea that the changed ratio is caused by the old rats' longer lives, an intensive 10-mo period of enrichment treatment was given to a group of animals, beginning at 3 mo of age. Compared with animals housed in standard cages, the enrichment treatment did not alter the glutamatergic response ratio measured with field potential recording methods. These data provide support for the conclusion that the observed change with age is developmentally regulated rather than experience dependent. Given the role of the NMDA_R in synaptic plasticity, these changes suggest a progressive commitment of perforant path synapses to particular weights over the life span. One possible implication of this effect includes preservation of selected memories, ultimately at the expense of a reduced capacity to store new information.