A study of cortical and hippocampal NMDA and PCP receptors following selective cortical and subcortical lesions

Abstract

The neuronal localization of glutamate and phencyclidine (PCP) receptors was evaluated in the cerebral cortex and hippocampal formation of rat CNS using quantitative autoradiography. Scatchard analysis of [3H]glutamate binding in the cortex (layers I and II and V and VI) showed no difference in the total number of binding sites (Bmax) or apparent affinity (Kd) 1 week, 1 month and 2 months following unilateral ibotenate lesions to nucleus basalis of Meynert (nbM) compared to the non-lesioned side. Quisqualic acid displacement of [3H]glutamate in layers I and II, 1 week following nbM destruction, revealed both high- and low-affinity binding sites (representing the quisqualate (QA) and (NMDA) sites, respectively). Compared to the control side, there was no difference in binding parameters for either of the receptors sites. In similarly lesioned animals, the NMDA receptor was specifically labelled with [3H]glutamate and the associated PCP receptor labelled with [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine ([3H]TCP) in adjacent brain sections. For both receptors, there was no change in the total number of binding sites in the cortex following destruction of nbM. On the other hand, virtually all binding to NMDA and PCP receptors was eliminated following chemical destruction of intrinsic cortical neurons. These results suggest that the NMDA/PCP receptor complex does not exist on the terminals of cortical cholinergic afferents. One week after knife cuts of the glutamatergic entorhinal pathway to the hippocampal formation only an approximate 10% reduction of NMDA and PCP receptors was seen in the dentate gyrus. Conversely, selective destruction of the dentate granule cells using colchicine caused a near identical loss of NMDA and PCP receptors (84% vs 92% respectively). It is concluded from these experiments that glutamate and PCP receptors exist almost exclusively on neurons intrinsic to the hippocampal formation and that no more than 10% of NMDA and PCP receptors exist as autoreceptors on glutamatergic terminals.