Abstracts

Transcranial freeze lesions in neonatal rat pups produce microgyri that can be used to model human cortical polymicrogyria. The cortical area surrounding the microgyrus (paramicrogyral zone, PMG) was previously found to be epileptogenic (Jacobs et al, 1996, 1999). Inhibitory and excitatory neurons located in rodent barrel cortex are known to form functional circuits mediating vibrissal sensation. Here, we examined the hypothesis that reorganization of the barrel microcircuits occurs in the PMG, leading to sensory evoked epileptiform discharges. We made transcranial freeze lesions in P0-P1 rats, resulting in single microgyral malformations that extended over 1-2 barrels in the face representation of the somatosensory cortex by P10. Thalamocortical slices were prepared according to methods described by Agmon and Connors. Dual whole-cell patch-clamp recordings were made from identified neurons in the barrel. Extracellular multiple-unit activities were recorded from cortex using monopolar tungsten electrodes and a Grass amplifier (bandwidth, 0.3-10 kHz). Bipolar extracellular stimuli were delivered to the VB nucleus through sharpened tungsten electrodes. (1) Single electrical stimuli applied to the thalamic VB nucleus evoked transient cortical multiunit activity (65+/-42 ms) in untreated thalamocortical (TC) slices from naive rats and robust paroxysmal discharges (850+/-100 ms) in similar slices from freeze lesioned cortex. (2) The epileptiform discharges originated from the PMG and propagated laterally, with a latency of about 100 ms, over a distance of about 5 mm. (3) The discharges were occasionally highly synchronous between two adjacent recording sites ([lt]0.5 mm), and had a complex frequency spectrum including alpha, beta and gamma bands. (4) Paroxysmal discharge duration was significantly shortened by about 70% when slices were perfused with ACSF containing APV, and epileptiform activity was totally abolished by CNQX. (5) The cortical paroxysmal discharges did not evoke thalamic oscillations in TC slices (n = 5). (6) Raising [K⁺][sub]o[/sub] from 2.5 to 5 mM and adding glutamine (0.3 mM) increased the incidence of spontaneously occurring cortical bursts discharges and the duration of the paroxysmal oscillations by 25%, and shortened the latency for horizontal propagation by 35%. (7) Dual whole-cell patch-clamp recordings from layer 4 of barrel cortex showed a selective loss of inhibition from a subgroup of interneurons. (1) Reorganization of the barrel microcircuits occurs in the PMG, leading to sensory evoked epileptiform discharges. (2) Inhibitory networks in the PMG are preferentially affected. Selective loss of inhibition from a subgroup of interneurons was likely a major factor leading to unconstrained cortical recurrent excitation and epileptiform activity in the somatosensory cortex. (Supported by NIH grant NS06477 and NS12151 from the NINDS.)