Electrophysiologic and pharmacologic characterization of serotonergic receptor subtypes in the deep cerebellar nuclei

Based on anatomical studies demonstrating a serotonergic (5-HT) innervation to the deep cerebeUar nudei (DCN) and autoradiographic study that identified at least three 5-HT receptor subtypes in the DCN, the present electrophysiological studies utilizing an in-vitro cerebellar slice preparation were designed to address three major objectives: (1) the actions of 5-HT or neurons of the dentate/interpositus nudei, (2) the receptor subtypes responsible for mediating effects of 5-HT, and (3) the potential role of adenylate cydase as a transducer of inhibitory effects of 5-HT.

Superfusion and iontophoretic appUcation of 5-HT caused either exdtation or inhibition of the spontaneous activity of dentate/interpositus neurons. Studies utilizing selective agonists and antagonists for 5-HT receptor subtypes revealed that the 5-HTiA receptor subtype is responsible part, for mediating 5-HT-induced inhibition. In addition, the 5-HT2 receptor subtype elicits indirect inhibition presumably by activation of GABAergic intemeurons. These studies also demonstrated that the 5-HT4 receptor subtype is responsible for mediating exitatory and inhibitory effects of 5-H

Data from experiments utilizing compounds that affect the adenylate cyclase second messenger cascade at various stages indicated that these receptor subtyp>es are potentiaUy negatively coupled to adenylate cydase. Sp)ecificaUy, inhibitory effects eUdted by activation of 5-HTi A and 5-HT4 receptor subtypes mediate inhibition possibly via a decrease in activity of s- adenylate cydase-dependent system in these neurons.