5-HT modulates synaptic transmission in vestibular nucleus of rats

Abstract

Serotonergic projections from the raphe nucleus are known to innervate the medial vestibular nucleus (MV). Acute administration of serotonin (5-HT) to rat MV was found to prolong the execution time in balance beam test and in negative geotaxis, a behavioral indicator of gravity detection. To delineate the effect of 5-HT on neurotransmission within MV, whole-cell patch-clamp recording was conducted in brainstem slices of P14 rats. Both excitatory and inhibitory synaptic transmission were examined. In most MV neurons receiving glutamatergic input, 5-HT reduced the amplitude of evoked excitatory postsynaptic currents (eEPSC) and this effect was mimicked by 5-HT1A receptor agonist. On the other hand, 5-HT exerted differential effect on GABAA receptor-mediated inhibitory transmission within MV. In one subgroup of MV neurons, 5-HT suppressed the amplitude of evoked inhibitory postsynaptic currents (eIPSC) via 5-HT1A receptor. In another subgroup of MV neurons, 5-HT enhanced the amplitude of eIPSC. This effect could be mimicked by 5-HT2A receptor agonist but blocked by 5-HT2A receptor antagonist. With a paired-pulse stimulation paradigm, we found that all the aforementioned effects of 5-HT on either eEPSC or eIPSC were accompanied by change in paired-pulse ratio. This suggests that the 5-HT induced effects within the MV are mediated via the activation of presynaptic 5-HT receptors. Together, our results indicate that 5-HT plays a heterogeneous role in modulating excitatory and inhibitory transmission within the MV circuitry, thereby contributing to vestibular-related behavioral outcome.