Laminar pattern of synaptic inhibition during convulsive activity induced by 4-aminopyridine in neocortical slices

Abstract

1. Epileptiform activity was induced in rat neocortical brain slices by application of a low concentration (10 microM) of 4-aminopyridine (4-AP). In intracellular recordings from regular spiking neurons, the activity was characterized by prolonged, all-or-none depolarizing events, with variable delay to a threshold stimulus. 2. At this concentration, 4-AP had no measurable effect on passive electrical properties or on action-potential characteristics. 3. Paroxysmal responses in neurons of deeper layers differed markedly from those of superficial cells. In deep neurons, responses resembled those generated by neocortical neurons exposed to GABAergic blockers. A low-intensity stimulus to the white matter evoked an excitatory postsynaptic potential (EPSP) that was followed with variable latency by a paroxysmal depolarizing shift that reversed at suprathreshold membrane potentials and upon which superimposed repetitive firing was always evident. By contrast, in superficial (layer II-III) neurons, the same stimulus evoked an EPSP that was followed by a prolonged response whose late component reversed at subthreshold membrane potentials (between -50 and -80 mV). These cells rarely fired more than a single spike throughout the response. 4. Repetitive stimulation at relatively low frequencies (0.3-1 Hz) caused a gradual change in the synchronized responses that was most marked in superficial neurons. The reversal potential of the response shifted toward suprathreshold membrane potentials, and subsequently, superimposed repetitive firing became evident. These changes were not associated with measurable changes in input resistance or membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)