Comparison of neuronal response patterns in the external and central nuclei of inferior colliculus during ethanol administration and ethanol withdrawal

Abstract

Convulsive seizures during ethanol withdrawal (ETX) in rodents can be precipitated by acoustic stimulation. The inferior colliculus (IC) is strongly implicated in the neuronal network for these audiogenic seizures (AGS) in animals undergoing ETX. Previous evidence indicates that the central nucleus of IC (ICc) is important in AGS initiation in ETX, but the ICc does not project directly to motor pathways. The external nucleus of IC (ICx) receives convergent output from a broad range of ICc neurons, which is not tonotopically organized, and projects to several nuclei with major motor connections. Lesion, neuroanatomical, and stimulation experiments suggest the involvement of the ICx in the AGS network in several forms of AGS, including ETX. The present study examined ICx neuronal firing patterns in awake behaving rats during ethanol administration and during ETX to examine the role of this structure directly. ICx neuronal responses during both ethanol intoxication and ETX were significantly suppressed as compared to pre-ethanol responses. ICx neuronal responsiveness was reduced (habituated) at faster (>0.25 Hz) rates of stimulus presentation. However, immediately prior to the onset of AGS, there was an increase in ICx neuronal responses that continued into the wild running phase of AGS. This increase in neuronal responses temporally corresponded to the sustained ICc neuronal responses during ETX just prior to AGS. The enhanced ICx neuronal responsiveness may be mediated, in part, by changes in GABA and glutamate receptor regulation previously observed during ETX. The net result of these changes involves a functional reversal of response habituation normally observed in ICx neurons. These data illuminate the nature of the changes in ICx neuronal function that serves to transmit the sensory input that originates in the ICc and propagates seizure to the brainstem AGS network nuclei responsible for the convulsive motor behaviors of ETX seizures.