ELECTROPHYSIOLOGY OF CA1 PYRAMIDAL NEURONS IN AN ANIMAL-MODEL OF NEURONAL MIGRATION DISORDERS - PRENATAL METHYLAZOXYMETHANOL TREATMENT

Prenatal methylazoxymethanol acetate (MAMac) injection disrupts cell m igration in developing rats. We investigated the electrophysiological characteristics of hippocampal CA1 pyramidal neurons from young MAMac- treated animals (postnatal days 25-35). In vitro intracellular recordi ngs from CA1 cells in MAMac-treated tissue revealed resting membrane p otential (mean, -61.5 +/- 1.5 mV), action potential amplitude (mean, 6 9 +/- 3.1 mV), action potential duration (mean, 2.1 +/- 0.2 ms), input resistance (mean, 51.5 +/- 3.6 M Omega) and time constant (mean, 33.2 +/- 1.2 ms) similar to those of CA1 cells from control tissue. Howeve r, MAMac-treated tissue could be distinguished as having a higher perc entage of cells (62% vs. 10%) which fire a burst of action potentials in response to suprathreshold current injection. The synaptic response s of CA1 cells in MAMac-treated and control tissue were comparable. Th e CA1 field response to stimulation was also comparable at all stimulu s intensities tested (50-1500 mu A). Elevation of extracellular potass ium concentration ([K+](0)) from 3 mM to 6 mM resulted in epileptiform discharge activity in response to stratum radiatum stimulation in all MAMac-treated slices (10/10) but in only one-third of controls (3/9). Spontaneous epileptiform discharges were also observed in the majorit y (8/13) of MAMac-treated slices bathed in 6 mM KCI but in no controls . These data suggest that MAMac treatment during fetal development not only disrupts normal anatomical organization but also leads to altera tions in electrophysiological features of the hippocampal CA1 pyramida l cell region. As such, the MAMac model may provide insights into earl y onset seizure syndromes associated with developmental abnormalities.