Abstract
Ethanol (EtOH) modulates synaptic efficacy in various brain areas, including the cerebellum, which acts for the motor learning and memory. Previous studies have reported that EtOH exposure enhances tonic inhibition of cerebellar granule cells, which is thought to be a major reason for alcohol-induced impairment of motor behavior. However, the effects of EtOH on molecular layer interneurons (MLIs), such as basket and stellate cells in the mouse cerebellum have remained unknown. Here, we found that a sedative EtOH concentration (50 mM) efficiently enhanced spontaneous activity of MLIs and increased their firing rate. The EtOH-mediated excitation was blocked by inhibitors for adenylyl cyclase and the hyperpolarization-activation cation current, Ih, suggesting that the HCN channels were activated by EtOH. Furthermore, an anesthetic EtOH concentration (100 mM) induced facilitation of miniature IPSCs, which was mainly dependent on intracellular cyclic AMP, voltage-dependent Ca2+ channels, and intracellular Ca2+ stores, but not on Ih or PKA. Therefore, EtOH enhances GABAergic transmission onto Purkinje cells through Ih-dependent facilitation of MLI firing, and cyclic AMP-regulated and PKA-independent enhancement of Ca2+-triggered GABA release at presynaptic terminals. This dual modulation of GABAergic synaptic transmission could influence spontaneous activity of cerebellar Purkinje cells, leading to regulation of the cerebellar neuronal circuit processing. [J Physiol Sci. 2008;58 Suppl:S127]
