Ethanol Inhibits the Sensory Responses of Cerebellar Granule Cells in Anesthetized Cats

Abstract

Granule cells occupy a strategic position in the transmission of afferent information to the cerebellar cortex. They are also the most abundant type of neurons in the cerebellum. The functions of the cerebellum are thought to be sensitive to acute alcohol intoxication. The effects of acute alcohol intoxication on the in vivo physiology of cerebellar granule cells are, however, not completely known. We studied chloralose-anesthetized cats at ethanol doses relevant to human drinking (0.3-1.2 g/kg). We recorded the electrophysiological responses of granule cell clusters to auditory and visual stimulation, and simultaneously monitored the concentration of ethanol in the cerebrospinal fluid (CSF). At an intravenous ethanol dose of 0.3 g/kg, CSF ethanol concentration peaked in 10 minutes at 17 mM, equivalent to a blood alcohol concentration (BAC) of about 0.08 g/dL. Ethanol quickly and almost completely abolished both auditory and visual responses from granule cells. Complete or near-complete inhibition lasted 15 to 20 minutes; approximately 50% recovery required an additional 15 minutes, and a full recovery yet another 15 minutes. A higher ethanol dose at 1.2 g/kg resulted in a more severe inhibition and required longer time for recovery. The relationship between ethanol dose, CSF ethanol concentration, and granule cell responses was dynamic and nonlinear, critically depending upon the elapsed time. Cerebellar granule cell sensory responses are highly sensitive to ethanol inhibition. A rapid development of acute tolerance appears to be a major factor contributing to the dynamic and nonlinear relationship among ethanol dosage, CSF ethanol concentration, and granule cell responses. It is likely that a generalized de-afferentation of the cerebellum from its mossy fiber afferents, followed by the subsequent development of acute tolerance may play major roles by which alcohol intoxication affects cerebellar functions.