Alterations of inhibitory synaptic responses in the dentate gyrus of temporal lobe epileptic patients

Abstract

The number of orthodromically evoked population spikes was used to classify brain slice tissue from the dentate gyrus of temporal lobe epileptic patients as "more excitable" (multiple population spikes) or "less excitable" (a single population spike). During orthodromic stimulation, "more excitable" tissue exhibited less paired-pulse depression in comparison to "less excitable" tissue. During antidromic stimulation, both multiple population spikes and paired-pulse depression were observed in "more excitable" tissue. "Less excitable" tissue exhibited a single antidromic spike and often no antidromically evoked paired-pulse depression. The strength of antidromic paired-pulse depression was correlated positively with the number of antidromic spikes and was correlated negatively with orthodromic paired-pulse depression. Although orthodromic and antidromic paired-pulse depression were correlated to the number of orthodromically evoked population spikes, this correlation was not as strong as that between orthodromic paired-pulse depression, antidromic paired-pulse depression, and number of antidromically evoked population spikes. The antidromic paired-pulse depression observed in tissue exhibiting antidromically evoked multiple population spikes was enhanced rather than blocked by bicuculline. In addition, the blockade of the antidromic paired-pulse depression by CNQX indicated that this inhibition is mediated by an AMPA-type glutamatergic synapse. We suggest that alterations in circuitry occur in the dentate gyrus of some temporal lobe epileptic patients and were manifested by both a loss of inhibitory input as well as an increase of inhibition, which was dependent on the pathway of stimulation. The results of pairing antidromic and orthodromic stimuli were consistent with these conclusions.