Intracellular recordings were made from CA1 pyramidal cells in the hippocampal slice in vitro. The responses to orthodromic and antidromic activation and to ionophoretically applied GABA were studied. 2. The epileptogenic agent sodium benzyl penicillin reduced the recurrent i.p.s.p. evoked by subthreshold antidromic stimulation. Reversal potential studies of the i.p.s.p. and resistance measurements showed that this reduction was mainly due to a decrease in i.p.s.p. conductance. 3. Penicillin also reduced the conductance and associated membrane potential changes induced by ejecting GABA near the soma or into the apical dendritic region. 4. The mixed e.p.s.p.-i.p.s.p. evoked by orthodromic stimulation was converted to a pure depolarizing potential as the i.p.s.p. was blocked. Concurrently the probability of discharge to a constant orthodromic stimulus was increased. Similar changes were seen in a low chloride solution. 5. The time course of the reduction of inhibition was similar to that of the enhanced orthodromic response seen after penicillin treatment. 6. We conclude that reduction of postsynaptic inhibition is partly responsible for the increased probability of orthodromic discharge caused by penicillin. The longer latency all-or-nothing burst seen in some cells, however, seems to require an additional mechanism, although reduced inhibition may facilitate the triggering of this burst.
