REORGANIZATION OF BARREL CIRCUITS LEADS TO THALAMICALLY-EVOKED CORTICAL EPILEPTIFORM ACTIVITY.

We studied circuit activities in layer IV of rat somatosensory barrel cortex containing microgyri induced by neonatal freeze lesions. Structural abnormalities in GABAergic interneurons are present in the epileptogenic paramicrogyral area (PMG) and we therefore tested the hypothesis that decreased postsynaptic inhibition within barrel microcircuits occurs in the PMG and contributes to epileptogenesis when thalamocortical afferents are activated. In thalamocortical (TC) slices from naïve animals, single electrical stimuli within the thalamic ventrobasal (VB) nucleus evoked transient cortical multi-unit activity lasting 65±42 ms. Similar stimuli in TC slices from lesioned barrel cortex elicited prolonged 850 ±100 ms paroxysmal discharges that originated in the PMG and propagated laterally over several mm. Paroxysmal discharges were shortened in duration by ~70 % when APV was applied, and were totally abolished by CNQX. The cortical paroxysmal discharges did not evoke thalamic oscillations. Whole cell patch clamp recordings showed that there was a shift in the balance of TC evoked responses in the PMG that favored excitation over inhibition. Dual whole-cell recordings in layer IV of the PMG indicated that there was selective loss of inhibition from fast-spiking interneurons to spiny neurons in the barrel circuits that likely contributed to unconstrained cortical recurrent excitation with generation and spread of paroxysmal discharges.