Plastic response of hippocampal excitatory amino acid receptors to deafferentation and reinnervation

Abstract

In vitro autoradiography was used to examine the response of excitatory amino acid receptors in the hippocampus of rat following unilateral lesions of the entorhinal cortex. The density of N-methyl-D-aspartate and quisqualate receptor binding was determined on days 1, 3, 7, 14, 21, 30 and 60 postlesion both ipsilateral and contralateral to the lesion and in unoperated controls. The results are compared to the time-course of deafferentation and reinnervation. The molecular layer of the dentate gyrus contralateral to the lesion is only minimally denervated, but is known to exhibit extensive synapse loss and replacement. N-Methyl-D-aspartate receptor binding density in the contralateral hippocampus increased (10-15% relative to unoperated controls) as early as 3 days postlesion and remained elevated through all postlesion times examined. In contrast, the quisqualate receptors in the contralateral hippocampus were unaffected at all times investigated. In the deafferented molecular layer of the ipsilateral dentate gyrus there was a small transient decrease (15-20%) in the binding density of quisqualate receptors 3 days postlesion. At later postoperative times (30-60 days postlesion) the density of both N-methyl-D-aspartate and quisqualate receptors in the ipsilateral molecular layer was higher (15-50%) than that of unoperated controls. These results indicate that N-methyl-D-aspartate and quisqualate receptors are differentially regulated in response to deafferentation. The rapid decrease in quisqualate (and perhaps also N-methyl-D-aspartate) receptor binding at 3 days postlesion may simply reflect the loss of presynaptic receptors, the turnover of postsynaptic receptors or the down-regulation of postsynaptic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)