Alcohol is a widely abused substance and is responsible for significant morbidity and mortality worldwide. The precise mechanisms underlying ethanol (EtOH)'s actions in the central nervous system (CNS) remain elusive. In vitro studies suggest that GABAergic interneurons are important targets of EtOH action in the CNS. Although EtOH generally acts to inhibit CNS neurons, it appears to cause an increase in GABAergic interneuron excitability. However, it has yet to be demonstrated that EtOH produces this effect in the brain of behaving animals. Here, we demonstrate for the first time that acute EtOH exposure excites a subtype of GABAergic interneuron (cerebellar Golgi cell [GoC]) in a freely moving animal.
Electrophysiological recordings were made from microwire arrays implanted in the anterior cerebellum of freely moving rats.
Cerebellar GoCs display a slow, irregular, spontaneous action potential firing pattern under control conditions. EtOH caused dramatic and consistent increases in the rate and regularity of GoC discharges, including a redistribution of the power in the GoC spike train, such that power became concentrated in the 26.7 ± 7.3 Hz region.
Taken together with our previous findings, these data suggest that a major mechanism of EtOH actions on cerebellar function is an EtOH-induced de-afferentation at the input stage of the cerebellar cortex in the form of granule cell inhibition, and that this inhibition is caused by an increase in GoC firing. It is likely that GoCs may play a significant role both in the gating of information transmission to granule cells and in the modulation of the overall excitability of the cerebellum by tonically controlling granule cell activity.
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