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

In vivo chronic partial isolation of neocortical islands results in epileptogenesis that involves pyramidal neurons of layer V. To test whether an alteration in glutamate receptors might contribute to the epileptiform activity, we analysed the time-course of light microscopic changes in expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors using subunit-specific antibodies. The isolation caused a rapid down-regulation of immunoreactivity for GluR1 and GluR2/3 subunits in deep layer V pyramidal neurons within the neocortical island which was evident 24h post-lesion, and 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 four weeks of survival, down-regulation of GluR2/3 and GluR2 involved the majority of pyramidal layer V neurons, except for cells in the upper part of layer 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 contrast to GluR2/3 immunoreactivity, NMDAR2A/B immunoreactivity was enhanced three weeks post-lesion. The present data provide evidence for plastic changes in glutamate receptors in neurons of partially isolated neocortical island. A sub-population of layer V neurons remains relatively unaffected, and would presumably be capable of generating fast glutamatergic synaptic potentials necessary for the development of synchronous epileptiform activity.