Neurosteroid modulation of neuronal excitability and synaptic transmission in the rat medial vestibular nuclei

In rat brainstem slices, we investigated the influence of the neurosteroids (NS) tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) on the synaptically driven and spontaneous activity of vestibular neurons, by analysing their effects on the amplitude of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation and on the spontaneous firing rate of MVN neurons. Furthermore, the interaction with GABA and glutamate receptors was analysed by using specific antagonists for GABAA (bicuculline), AMPA/kainate (NBQX), NMDA (AP5) and mGlu-I (AIDA) receptors. THDOC and ALLO evoked two opposite long-lasting effects, consisting of either a potentiation or a reduction of field potential and firing rate, which showed early and late components, occurring in conjunction or separately after NS application. The depressions depended on GABAA receptors, as they were abolished by bicuculline, while early potentiation involved glutamate AMPA/kainate receptors, since NBQX markedly reduced the incidence of early firing rate enhancement, and in the case of ALLO, even provoked depression. This suggests that THDOC and ALLO enhance the GABAA inhibitory influence on the MVN neurons and facilitate the AMPA/kainate facilitatory one. Conversely, a late potentiation effect, which was still induced after glutamate and GABAA receptor blockade, might involve a different mechanism. We conclude that the modulation of neuronal activity in the MVN by THDOC and ALLO, through their actions on GABAA and AMPA/kainate receptors, may have a physiological role in regulating the vestibular system function under normal conditions and during the stress response which accompanies many forms of vestibular dysfunction.