Mechanisms Of Ethanol Affects Sensory Stimulus-Evoked Response In Cerebelalr Granule Cell In Vivo In Mice

Objective:We here used electrophysiological and pharmacological methods to study the effects of ethanol on the sensory stimulation-evoked cerebellar granule cell (GC) field potential responses in vivo in mice. We aimed to investegate the possible mechanisms of the effects of ethanol on the sensory information transferred by cerebellar GCs, and to reveal a partial mechanism of sesory information integretion and transmission in cerebellar cortex.Methods:After ICR mice (6-8weeks) were anesthetized by intraperitoneal injection of urathane (1.3g/kg body weight i.p.), a1-1.5mm craniotomy were drilled to expose the cerebellar surface corresponding to cerebellar cortex Crus Ⅱ.The dura were removed, and the cerebellar surface was constantly superfused with oxygenated artificial cerebrospinal fluid (ACSF). Sensory stimuli were performed by air-puff (60ms,50-60psi) of ipsilateral whisker pad. The air-puf stimuli were controled by a computer and were synchrinized with electrophysiology recording. Field potential recording were employed to record the sensory stimuli evoked responses in cerebellar GC. The recording electrodes were filled with ACSF, with the resistance of4-6MΩ. Sensory stimulation evoked GC field potential responses were recorded by an Axopatch-1D amplifier and acquired using Clampex8.1software. Electrophysiological data were analyzed using Clampfit10.1software. Differences between the mean values recorded under control and test conditions were evaluated by Student’s paired t-test using SPSS software. Differences were considered significant at P<0.05.Results:(1) Under urathane anesthetized conditions, air-puff stimulation of ipsilateral whisker-pad evoked high fidelity responses in GCs of cerebellar Crus Ⅱ. which enpre stimulus-on response (P1) and stimulus-off response (P2).(2) Cerebellar surface purfusion of ethanol did not change the latency of the evoked responses, but reversible inhibited the sensory stinulation evoked responses in GCs. Application of50mM ethanol for10min, the normalized amplitude of P1was decreased by (9.9±1.9)%, and the normalized amplitude of P2was decreased by(13.7±4.7)%.(3) The ethanol-induced inhibition of the sensory stimulation-evoked responses was concentration-dependent. The minimal cocentration is0.5mM, and the maximal inhibitory concentration is300mM which induced a decrease in the the normalized amplitude of P1by (19.2±5.1)%.(4) High concentration of ethanol not only induced a decrease in the amplitude of P1, but also significantly decreased half-width, area, rise tau and decay tau of P1. (5) Blockade of GABAA receptor activity induced an increase in amplitude of P1. and abolished the ethanol induced inhibition in the sensory stimulation-evoked response of GC indicated that ethanol induced inhibition in cerebellar GC sensory responses via enhancement of GABAA receptors activity.Conclusions:Ethanol inhibited the sensory-stimulation evoked responses in cerebellar GCs through enhancement of GABA receptors activition, indicated that ethanol inhibited the cerebellar GCs to transfer sensory information. These results suggested that the impair of cerebellar motorial coordination by acute alcohol intoxication could be related to the ethanol induced inhibition of the cerebellar cortical sensory informatin transmission.