5-HT2A receptor mediated facilitation of inhibitory neurotransmission in medial vestibular nucleus

Abstract

Serotonergic projections from the raphe nucleus are known to innervate the medial vestibular nucleus (MVN). However, the role of this projection is yet to be determined. Whole-cell patch clamp technique was used to investigate serotonergic modulation of inhibitory neurotransmission on MVN neurons of rats. Perfusion of serotonin (5-HT) to brainstem slice containing the vestibular nucleus greatly increased the frequency and amplitude of spontaneous inhibitory postsynaptic currents of MVN neurons but did not change their rise time nor decay time. Administration of selective 5-HT2A receptor agonist could mimic the bursting effect of 5-HT and this was blocked by 5-HT2A receptor antagonist. Nevertheless, this enhancement of inhibitory transmission was not observed with the application of 5-HT1A, 5-HT1B or 5-HT3 receptor agonists. These demonstrate that inhibitory transmission within the MVN could be enhanced via 5-HT2A receptor but not other types of 5-HT receptors. Interestingly, this enhancement effect of 5-HT disappeared with the perfusion of tetrodoxin that blocked action potentials, suggesting that the effect of 5-HT on MVN neurons is mediated via presynaptic 5-HT receptors. Using GABAA receptor antagonist or glycine receptor antagonist, we further identified that both receptors took part in enhancing the inhibitory effects of 5-HT. Taken together, our results indicate that presynaptic 5-HT2A receptors function to facilitate both GABAA receptor- and glycine receptor-mediated inhibition of MVN neurons.