Abstracts

Rationale: Polymicrogyria is a developmental disorder of the neocortex that is associated with epilepsy. The paramicrogyral region (PMG) in clinical and experimental microgyria exhibits abberrant electrophysiological properties and epileptiform discharges can readily be evoked. Excitatory connectivity is increased in the PMG of experimental microgyria, but it is not known to which degree inhibitory connectivity is altered. Methods: Focal photolysis of caged glutamate using a UV laser pulse (laser scanning photostimulation, LSPS) was used to excite presynaptic cells and record resulting IPSCs. Regions up to 300 μm lateral to the recorded cell and including all cortical layers were scanned. Stimulation resulted in long- (10-50 ms) and short-latency (~5-10 ms) IPSCs (ll-IPSCs and sl-IPSCs, respectively). Both types of IPSCs were identified as GABAergic synaptic events based on stepwise increases in amplitude and or number with higher stimulation intensity and sensitivity to picrotoxin. sl-IPSCs were likely caused by glutamatergic activation of somata or terminals of fast spiking interneurons (FS interneurons), while ll-ISPCs were likely triggered by activation of more distant, mainly nonFS interneurons. Results: We compared amplitude and number of IPSCs in pyramidal cells in homotopic neocortex of control rats and in the PMG of freeze-lesioned rats. sl-IPSCs could only be evoked from locations close to the recorded cells’ soma, while ll-IPSCs could be evoked from a much wider cortical area and activation regions were not strictly centered on the recorded cells’ soma. sl-IPSCs in PMG pyramidal cells had significantly higher amplitudes than in control cells. ll-IPSCs, which were significantly smaller than sl-IPSCs, also had a tendency towards increase in PMG pyramidal cells, but it did not reach statistical significance. Conclusions: The perisomatic location of FS-pyramidal cell synapses, the low incidence of failures and the high amplitude of sl-IPSCs are ideally suited to rapidly and reliably veto action potentials in pyramidal cells. Activation of FS interneurons during epileptiform network events would provide strong inhibition to pyramidal cells, which might serve as a powerful means to limit spread of epileptiform activation. We speculate that upregulation of FS-pyramidal cell inhibition in PMG neocortex may be a compensatory mechanism to prevent seizure initiation/propagation.