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J Neurophysiol (April 16, 2008). doi:10.1152/jn.01276.2007
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01276.2007v1
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Submitted on November 21, 2007
Accepted on April 10, 2008

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

Zhiyong Yang1, Michael Krause1, Geeta Rao1, Bruce L. McNaughton2, and Carol A Barnes3*

1 ARL Division of Neural Systems, Univeristy of Arizona, Tucson, Arizona, United States
2 ARL Division of Neural Systems, University Of Arizona, Life Science North Bldg., Tucson, Arizona, 85724, United States; Evelyn F. McKnight Brain Institute, Univeristy of Arizona, Tucson, Arizona, United States; Department of Psychology, Univeristy of Arizona, Tucson, Arizona, United States; Department of Physiology, Univeristy of Arizona, Tucson, Arizona, United States
3 University of Arizona, Tucson, Tucson, Arizona, United States; Evelyn F. McKnight Brain Institute, Univeristy of Arizona, Tucson, Arizona, United States; Department of Psychology, Univeristy of Arizona, Tucson, Arizona, United States; Department of Neurology, Univeristy of Arizona, Tucson, Arizona, United States

* To whom correspondence should be addressed. E-mail: carol{at}nsma.arizona.edu.

Synaptic transmission in hippocampal field CA1 is largely NMDAR-dependent during the early post-natal period. It then becomes increasingly mediated by AMPA receptors until an adult ratio of AMPA to NMDA receptors is achieved. It is shown here that increases in the AMPAR-mediated field potential response continue over the lifespan of the F-344 rat at the perforant path-granule cell synapse in the dentate gyrus. By contrast, the NMDAR-dependent component of the response decreases with age between 1 and 27 months, leading to an increase of AMPAR/ NMDAR ratio with age. One possible explanation of this age difference is that the AMPAR/ NMDAR ratio can be modifiable by experience. To test the idea that the changed ratio is due to the old rats' longer lives, an intensive 10 month period of enrichment treatment was given to a group of animals, beginning at 3 months of age. Compared to 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 NMDAR in synaptic plasticity, these changes suggest a progressive commitment of perforant path synapses to particular weights over the lifespan. One possible implication of this effect includes preservation of selected memories, ultimately at the expense of a reduced capacity to store new information.







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