THE SYNAPTIC ACTIVATION OF N-METHYL-D-ASPARTATE RECEPTORS IN THE RAT MEDIAL VESTIBULAR NUCLEUS

1. We examined the synaptic activation of N-methyl-D-aspartate (NMDA) receptors by stimulation of primary vestibular afferent projections to second-order neurons in the medial vestibular nucleus (MVN) using who le cell patch-clamp recording methods in rat brain stem slices maintai ned in vitro. 2. Stimulation of the vestibular nerve (nVIII) evoked mo nosynaptic excitatory postsynaptic potentials (EPSPs) in second-order MVN neurons. Bath application of the gamma-aminobutyric acid receptor antagonist bicuculline (10 mu M) revealed a late, slow EPSP that was b locked by the NMDA receptor antagonist D-2-amino-5-phosphonovalerate ( D-AP5; 50 mu M)and displayed a voltage-dependent reduction at hyperpol arized potentials in the presence of external magnesium (1 mM). The ea rly component of the nVIII-evoked EPSP in the presence of bicuculline was blocked by the lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 mu M) and displayed linear current-voltage relations in the presence of external magnesium. 3. In some cells both components of the EPSP were blocked by DNQX, whereas only the late component was sensitive to D-AP 5, indicating that NMDA receptors also mediate excitation via intrinsi c pathways within MVN. 4. The NMDA receptor-mediated excitatory postsy naptic current (EPSC) evoked by nVIII stimulation was recorded in volt age-clamped MVN neurons in a magnesium-free saline containing bicucull ine (10 mu M) and DNQX (10 mu M). At -80 mV the NMDA receptor-mediated EPSC (latency = 2.7 ms) displayed a slow rise time (10-90%, 5.8 ms) a nd exhibited a biexponential decay [time constant of fast component of decay (tau(f)) = 27.6 ms, time constant of slow component of decay (t au(s)) = 147.4 ms]. Neither the rise time of the EPSC nor the time con stants of decay exhibited any degree of voltage dependence over the ra nge of -90 to +50 mV. 5. The results demonstrate that NMDA receptors o n second-order vestibular neurons participate both in the direct synap tic response to primary afferent stimulation and in excitatory transmi ssion within the intrinsic circuitry of MVN. Synaptic activation of NM DA receptors within the vestibular nuclear complex may contribute to t he proposed role of NMDA receptors in vestibular compensatory mechanis ms.