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. The gradual recovery and subsequent increase over control values in the binding density of both types of receptors at later postoperative times, however, suggest that long-term plastic compensatory processes take place in the hippocampus in response to deafferentation. The changes in the inner molecular layer and in the contralateral hippocampus indicate that the response of receptors is not restricted to the areas that are directly denervated. These adaptive responses may participate in the functional restoration of partially damaged circuitry.