Role of G-protein-coupled serotonin receptor on synaptic plasticity of excitatory transmission in the vestibular nucleus of rats

Abstract

Serotonergic projections from the raphe nucleus are known to innervate the medial vestibular nucleus (MV) but the contribution of serotonin in the vestibular system remains fragmentary. Acute administration of serotonin (5-HT) to the MV of P14 rats impaired the performance in rota-rod task, balance beam test and negative geotaxis. Whole-cell patch-clamp recording in MV neurons of brainstem slice preparations showed increase in the amplitude and frequency of spontaneous excitatory postsynaptic current (EPSC) with 5-HT treatment. Among G-protein-coupled 5-HT receptors that modulate synaptic plasticity in excitatory circuitries, we found 5-HT2 receptor (Gq-coupled) and 5-HT7 receptor (Gs-coupled) expressed in neurons of the vestibular nucleus. We then pursued the roles of these receptors in MV neurons. Treatment of MV neurons with agonist of the 5-HT7 receptor induced reduction in the amplitude of evoked-EPSC but not with agonist of the 5-HT2 receptor. With the use of combinations of single and dual agonist/ antagonist that target the Gs- and Gq-coupled 5-HT receptors, we further found that the suppression of NMDAR-dependent long-term depression in MV neurons was mediated by the 5-HT7 receptor but not by the 5-HT2 receptor. Aside from the PKA-dependent signaling cascade, downstream cross-talk with the PKC-dependent pathway was involved. Taken together, our results reveal that Gs- but not Gq-coupled serotonin receptors mediate the expression of long-term plasticity in excitatory synapses within the vestibular nucleus, and suggest their involvement in the expression of vestibular behaviors.