Nicotine depresses facial stimulation-evoked molecular layer interneuron-Purkinje cell synaptic transmission via α7 nicotinic acetylcholine receptors in mouse cerebellar cortex.

Nicotine modulates cerebellar physiology function by interacting with nicotinic acetylcholine receptors (nAChRs) and is involved in modulation of cerebellar cortical circuitry functions. Here, we investigated the effect of nicotine on sensory stimulation-evoked molecular layer interneuron-Purkinje cell (MLI-PC) synaptic transmission mouse cerebellar cortex using in vivo cell-attached recording technique and pharmacological methods. The results show that micro-application of nicotine to the cerebellar molecular layer significantly decreased sensory stimulation-evoked MLI-PC synaptic transmission in mouse cerebellar cortex. Nicotine-induced depression in sensory stimulation-evoked MLI-PC synaptic transmission was abolished by either a non-selective nAChR blocker, hexamethonium, or the α7-nAChR antagonist methyllycaconitine (MLA), but not the selective α4β2-nAChR antagonist dihydro-β-erythroidine. Notably, molecular layer micro-application of nicotine did not significantly affect the number of spontaneous or facial stimulation-evoked action potentials of MLIs. Moreover, nicotine produced significant increases in the amplitude and frequency of miniature inhibitory postsynaptic currents of PCs, which were abolished by MLA in cerebellar slices. These results indicate that micro-application of nicotine to the cerebellar molecular layer depresses facial stimulation-induced MLI-PC synaptic transmission by activating α7 nAChRs, suggesting that cholinergic inputs modulate MLI-PC synapses to process sensory information in the cerebellar cortex of mice in vivo.