In vitro electrophysiological properties of inferior colliculus cortex neurons in genetically epilepsy-prone rats and rats undergoing ethanol withdrawal.

摘要

Genetically epilepsy-prone rats (GEPRs) and rats during ethanol withdrawal (ETX) exhibit audiogenic seizures (AGS). The inferior colliculus (IC) is critical for seizure initiation in both AGS forms. The major subdivisions of IC are the central nucleus (ICc), external cortex (ICx), and dorsal cortex (ICd). The ICc is critical in AGS initiation point, but IC cortex may also be critical in AGS.;In vitro intracellular recordings were made from IC cortex in slice, and afterhyperpolarization, anode break potentials, potassium mediated membrane rectification and calcium mediated depolarization were observed in normal neurons. Most neurons exhibited sustained firing during depolarization. Stimulation of the commissure of the IC (CoIC) produced varying combinations of EPSPs and IPSPs in the same neurons, revealing the convergence of excitatory and inhibitory influences on IC cortex neurons. Pharmacological studies indicated that NMDA receptors mediate slow EPSPs and non-NMDA receptors mediate fast EPSPs. Bicuculline, a GABA-A receptor antagonist, abolished most IPSPs. Some physiologically evaluated neurons were intracellularly stained with biocytin and found to have multipolar shapes.;The changes of membrane and synaptic properties in GEPRs and during ETX were recorded in IC cortex. These include (1) reduced action potential threshold, (2) increased incidences of anode break response, (3) epileptiform responses, and (4) spontaneous action potentials, which could promote seizure development. Stimulation of the ColC caused a high incidence of paired pulse facilitation in IC cortex neurons in GEPRs and during ETX, while paired pulse inhibition occurred in normal neurons. In a group of GEPRs that never experienced AGS, IC cortex neurons exhibited reduced action potential threshold, while there was a trend to increased incidences of epileptiform activity and spontaneous activity, suggesting that these abnormalities may relate to seizure predisposition. However, no increase in paired pulse facilitation or anode break responses was observed in non-stimulated GEPRs, suggesting that these abnormalities may relate to seizure experience.;Our pharmacological and EPSP data indicate that AGS susceptibility involves decreased GABAergic inhibition and enhanced glutamatergic excitation in IC cortex. These results suggest that abnormal IC excitability and altered amino acid neurotransmission in the IC cortex neurons contribute to seizure predisposition and AGS initiation in AGS-susceptible animals.