Dysplastic Cortex (DC) and periventricular neuronal heterotopia (PNH) are commonly associated with medically intractable forms of epilepsy in humans. Brain slices from rats exposed to irradiation in utero demonstrate DC and PNH coupled with an increased propensity for epileptiform bursting. We propose to study connections between PNH and DC and the relative contributions of these areas to epileptogenesis. Hypothesis 1: PNH will have reciprocal axonal connections with overlying DC. We will use antero and retrograde tracers to stain afferent and efferent projections of PNH and DC, providing histological evidence for interconnectivity. In the next set of experiments we will use a series of electrophysiological studies to determine how PNH integrates into the local cortical circuit. Hypothesis 2: PNH maintains functional anatomical connections with DC. This hypothesis may be tested by selective stimulation of neurons in PNH, while recording evoked postsynaptic currents in DC using whole-cell patch-clam and field potential configurations. We will then repeat the studies simulating in DC and recording evoked potentials in PNH. Hypothesis 3: DC, but not PNH, may sustain spontaneous epileptiform bursts because of its homology with layer V in the normal neocortex. Disinhibited neocortical slices will show synchronized epileptiform bur4ests in both PNH and DC as long as the two areas are functionally connected. Once functionally disconnected from DC, the quality of spike activity in PNH should change. Our long term goal is to use the information gained from these experiments to make the treatment of epilepsy safer and more effective in patients.
