Changes in AMPA receptor binding and subunit messenger RNA expression in hippocampus and cortex in the pentylenetetrazole-induced 'kindling' model ofepilepsy

"Kindling' is a phenomenon of epileptogenesis, which has been widely used a s an experimental model of temporal lobe epilepsy. In the present study, we have examined the contribution of alpha -amino-3-hydroxy-5-methylisoxazole -4-propionic acid (AMPA) glutamate receptors and their subunits (GluR-A, -B , -C and -D) to the acquisition and maintenance of the kindled state in the pentylenetetrazole (PTZ)-induced 'kindling' mouse model, by using quantita tive autoradiography and in situ hybridization. Region-specific increases i n [H-3]AMPA binding were seen in kindled animals in the CA3 region of hippo campus and in the temporal cortex 1 week after the last PTZ injection. At t he same time, a significant decrease in the level of transcripts encoding t he GluR-B and -C subunits was detected in the hippocampal CA1 region and de ntate gyrus, suggestive of a higher proportion of Ca2+-permeable AMPA recep tors in these neurons.' These changes did not persist 1 month after establi shment of kindling, indicating a transient role of AMPA receptors in the ac quisition of the kindled state. At 1 month after the last PTZ injection, an upregulation in [H-3]AMPA binding appeared in the motor cortex and the bas al ganglia of kindled animals, which is consistent with electrophysiologica l data showing hyperexcitability in the cortex of the PTZ-kindled animals a t that time. Interestingly, an increase in mRNA for the GluR-B subunit appe ared in the outer layers of motor and somatosensory cortices of the kindled animals 1 month after acquisition of the kindled state, possibly as part o f a gene-regulated, compensatory mechanism against seizure susceptibility, since this change should give rise to a higher proportion of Ca2+-impermeab le AMPA receptors. These results support the evidence of a transient role o f hippocampal AMPA receptors in the acquisition of the `kindling' phenomeno n and they also suggest an involvement of AMPA receptors in the maintenance of kindled state at least in two brain areas, cortex and basal ganglia. (C ) 2001 Published by Elsevier Science BY.