Changes of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptorsin layer V of epileptogenic, chronically isolated rat neocortex

In vivo chronic partial isolation of neocortical islands results in epilept ogenesis that involves pyramidal neurons of layer V. To test whether an alt eration in glutamate receptors might contribute to the epileptiform activit y, we analysed the time-course of Light microscopic changes in expression o f alpha -amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors using su bunit-specific antibodies. The isolation caused a rapid down-regulation of immunoreactivity for GluR1 and GluR2/3 subunits in deep layer V pyramidal n eurons within the neocortical island which was evident 24 h post-lesion, an d within three days was reduced to about 40-60% of the control level. Many pyramidal cells in deep layer V completely lacked GluR2. Between one and fo ur weeks of survival, down-regulation of GluR2/3 and GluR2 involved the maj ority of pyramidal layer V neurons, except for cells in the upper pan of la yer V, and those within narrow areas of all sub-laminae of layer V ("micro- islands"). Initial down-regulation was also observed one to three days post -lesion for subunits 1 and 2 of the N-methyl-D-aspartate receptor, but in c ontrast to GluR2/3 immunoreactivity, NMDAR2A/B immunoreactivity was enhance d three weeks post-lesion. The present data provide evidence for plastic changes in glutamate receptor s in neurons of partially isolated neocortical island. A sub-population of layer V neurons remains relatively unaffected, and would presumably be capa ble of generating fast glutamatergic synaptic potentials necessary for the development of synchronous epileptiform activity. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.