Presynaptic GABAA Receptors Mediate Ethanol-Induced Suppression at a Central Auditory Synapse

Abstract

Acute alcohol consumption impairs speech perception, particularly in noisy environments, but the synaptic mechanisms underlying this auditory deficit remain unknown. Here, we investigated how low-dose ethanol modulates the endbulb of Held synapse in the Mongolian gerbil cochlear nucleus, the first central relay of the auditory pathway. In vivo recordings showed that ethanol suppresses sound-evoked firing, an effect blocked by GABAA receptor antagonists. Direct presynaptic patch-clamp recordings revealed that ethanol potentiates GABAA currents at the endbulb of Held terminal but not at the postsynaptic spherical bushy cell. A high intra-terminal chloride concentration drives a GABA-mediated depolarization that activates low-threshold Kv1 potassium channels and shunts the presynaptic action potential. The reduced action potential amplitude limits calcium influx and glutamate release, effectively suppressing synaptic transmission. These findings identify ethanol-enhanced presynaptic shunting inhibition at the first central auditory synapse as a cellular mechanism for alcohol-induced auditory dysfunction.