5-HT-triggered facilitation of neurotransmitter release in medial vestibular nucleus

Abstract

Serotonergic projections from the raphe nucleus are known to innervate the medial vestibular nucleus (MV). However, the role of this projection has not been determined. To address this issue, whole-cell patch-clamp and double-immunostaining methods were used to investigate the serotonergic modulation of spontaneous synaptic transmission within the MV of young rats. Perfusion of serotonin (5-hydroxytryptamine, 5-HT) to brainstem slices greatly facilitated spontaneous inhibitory postsynaptic currents (sIPSCs) in a subgroup of MV neurons. That this enhancement effect of 5-HT on sIPSCs was abolished with blocker of spontaneous action potentials indicates that 5-HT acts on the somatodendritic area of presynaptic neurons. Using GABAA or glycine receptor antagonist, we further identified that both receptors took part in the enhancement effect of 5-HT on sIPSCs. This facilitatory effect could be mimicked with the administration of 5-HT2 receptor agonist but was blocked with 5-HT2A receptor antagonist. Similar operation was observed for serotonergic regulation of spontaneous postsynaptic currents (sEPSCs) in the MV circuitry. 5-HT significantly increased both the amplitude and frequency of sEPSCs. This 5-HT-induced enhancement of sEPSCs also depended on action potential. Such an enhancement of sEPSCs disappeared with AMPA receptor antagonist. 5-HT2 receptor agonist could mimic the 5-HT-induced facilitatory effect whereas use of a 5-HT2A receptor antagonist blocked the effect. Our results therefore indicate that within the MV, 5-HT2A receptors expressed on presynaptic neurons function to facilitate both inhibitory and excitatory neurotransmitters release.