Inhibition in penicillin-induced epileptic foci

Abstract

A previous study indicated that the early surface negative component (associated with recurrent inhibition) of the evoked potential recorded from cat pericruciate cortex, subsequent to pyramidal tract stimulation, was altered after application of penicillin to the cortical surface (Van Duijn et al. 1973). This suggested that decreased effectivess of recurrent inhibition might be the basis for epileptogenicity of penicillin.To verify that recurrent inhibition is functionally decreased in the penicillin epileptic focus and to assess alternative sites for penicillin action, this phenomenon was investigated at the cellular level. Neurons were recorded extracellularly and response to stimuli monitored throughout the transition from normal cortex to epileptogenic cortex. Stimuli employed were peduncular stimulation (to test recurrent inhibitory pathways), epicortical stimulation (to test inhibitory pathways, bypassing the recurrent collateral system), and forepaw footpad shock (to test the responsiveness of neurons to afferent input).In normal cortex, PT cells were inhibited by peduncular or epicortical stimulation and excited by forepaw stimulation, with the excitation followed by a period of inhibition. In the penicillin focus, inhibition was not observed in response to any of the 3 stimuli, and the excitatory response to forepaw stimulation was maintained.The bursting non-PT cells, most likely candidates for interneurons, exhibited excitation in response to peduncular and epicortical stimulation, consistent with involvement in inhibitory pathways. Nonetheless, in the penicillin focus, excitatory response to peduncular and epicortical stimulation was maintained. Excitatory response to forepaw stimulation was also maintained in the penicillin focus.The results demonstrate a loss of effectiveness of recurrent inhibition measured at the PT cell body in the penicillin focus. Further, the reduction in inhibitory feedback occurs in conjuction with maintained or enhanced excitability of the neurons which are most likely candidates for inhibitory interneurons. Thus, penicillin is most likely exerting its effect at the inhibitory synapses onto PT cells in the cortex, thereby allowing excitatory input to have greater influence on neuronal firing.