Medial vestibular neurons are endogenous pacemakers whose discharge is modulated by neurotransmitters

1. Neurons in the medial vestibular nucleus (MVN), recorded in a rat brain slice preparation, exhibit a highly regular, high-frequency (5- to 35-Hz) spontaneous discharge. The rhythmic firing rate was constant (< 5% variation) and sustained for a long time (maximum observation, 4 hr). 2. The rhythmic firing was evident even in neurons (n = 15) completely isolated from exogenous input fibers, suggesting that it is due to an endogenous pacemaker property. When recorded intracellularly, the discharge was found to be associated with a smooth, concave pacemaker prepotential, and the rate of firing was reduced in proportion to applied hyperpolarizing current, indicating that these are pacemaker discharges. 3. This conclusion is supported by the observation that perfusion with a low-calcium/high-magnesium Krebs-Ringer solution, which completely and reversibly blocks all synaptic transmission, did not abolish the spontaneous discharge. The low-calcium/high-magnesium solution increased spontaneous firing in some neurons and decreased in others, suggesting that the firing is synaptically modulated and the synaptic influence is tonically active. 4. Application of kynurenate (10 mM), an antagonist of the excitatory amino acid receptors, gradually reduced neuronal discharges in most neurons (22 of 25), while the addition of 10 mM sucrose as an osmotic control had no effect. Depression of neuronal discharges reached its minimum (an average of 60% of the control level) and was maintained at that level until gradually washed out. The rhythmic firing pattern persisted in all neurons even after the excitatory receptors were blocked. 5. When the GABAA receptor antagonist, bicuculline (20 microM), was applied, elevation of neuronal discharges was evident in most neurons (30 of 32) tested. The firing increased gradually, with a final control level of 130% (121-160%). In contrast, the GABAB receptor antagonist, phaclofen (20 microM and 100 microM), had no effect in most neurons (19 of 23) tested. Further, the excitatory and inhibitory action could be detected on the same neuron when bicuculline and kynurenate were both evaluated (n = 10). 6. These results indicate that the spontaneous discharge of MVN neurons is due to an endogenous pacemaker under the tonic influence of both inhibitory and excitatory transmitter actions. The bicuculline-sensitive GABAA receptors and the kynurenate-sensitive glutamate receptors both mediate the tonic modulation.