Inferior colliculus intracellular response abnormalities in vitro associated with susceptibility to ethanol withdrawal seizures

Abstract

During ethanol withdrawal (ETX), rats become susceptible to audiogenic seizures in which the inferior colliculus (IC) is known to play a critical role. The present study examined changes in membrane properties that occurred in IC dorsal cortex (ICd) neurons in brain slices from rats after 4 days of three times daily intragastric ethanol, which is proposed to be an analog of binge drinking. Compared with neurons from control animals, ICd neurons during ETX had action potentials (APs) with lower thresholds, a greater incidence of spontaneous APs, a reduced degree of spike firing adaptation, and an increased incidence of anode-break firing. With synaptic stimulation, epileptiform firing was seen in nearly 50% of ICd neurons during ETX but never was seen in normal ICd neurons except after perfusion of the gamma-aminobutyric acid type A (GABA(A)) antagonist bicuculline. Paired pulse responses of ICd neurons were also abnormal during ETX. Thus, in 75% of normal rats, paired synaptic stimuli inhibited the second response, but during ETX all neurons tested showed paired pulse facilitation. These aberrant membrane and synaptic properties provide direct evidence for the hyperexcitability of IC neurons during ETX. They may be due, in part, to changes in GABAergic and glutamatergic neurotransmission known to be produced during withdrawal after continued ethanol administration.