Reduced inhibition during epileptiform activity in the in vitro hippocampal slice.

Abstract

Intracellular recordigs were made from guinea pig CA1 pyramidal cells in a hippocampal slice in vitro. The responses to orthodromic and antidromic activation and to ionophoretically applied GABA were studied. The epileptogenic agent sodium benzyl penicillin reduced the recurrent ipsp[inhibitory postsynaptic potential]evoked by subthreshold antidromic stimulation. Reversal potential studies of the ipsp and resistance measurements showed that this reduction was mainly due to a decrease in ipsp conductance. Penicillin reduced the conductance and associated membrane potential changes induced by ejecting GABA near the soma or into the apical dendritic region. The mixed epsp[excitatory postsynaptic potential]-ipsp evoked by orthodromic stimulation was converted to a pure depolarizing potential as the ipsp was blocked. Concurrently the probability of discharge to a constant orthodromic stimulus was increased. Similar changes were seen in a low chloride solution. The time course of the reduction of inhibition was similar to that of the enhanced orthodromic response seen after penicillin treatment. Reduction of postsynaptic inhibition apparently is partly responsible for the increased probability of orthodromic discharge caused by penicillin. The longer latency all-or-nothing burst seen in some cells seems to require an additional mechanism, although reduced inhibition may facilitate the triggering of this burst.