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 whole cell patch-clamp recording methods in rat brain stem slices maintained in vitro. 2. Stimulation of the vestibular nerve (nVIII) evoked monosynaptic excitatory postsynaptic potentials (EPSPs) in second-order MVN neurons. Bath application of the γ-aminobutyric acid receptor antagonist bicuculline (10 μM) revealed a late, slow EPSP that was blocked by the NMDA receptor antagonist D-2- amino-5-phosphonovalerate (D-AP5; 50 μM) and displayed a voltage-dependent reduction at hyperpolarized potentials in the presence of external magnesium (1 mM). The early component of the nVIII-evoked EPSP in the presence of bicuculline was blocked by the α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 μM) 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-AP5, indicating that NMDA receptors also mediate excitation via intrinsic pathways within MVN. 4. The NMDA receptor-mediated excitatory postsynaptic current (EPSC) evoked by nVIII stimulation was recorded in voltage-clamped MVN neurons in a magnesium-free saline containing bicuculline (10 μM) and DNQX (10 μM). At -80 mV the NMDA receptor-mediated EPSC (latency = 2.7 ms) displayed a slow rise time (10-90%, 5.8 ms) and exhibited a biexponential decay [time constant of fast component of decay (τ(f)) = 27.6 ms, time constant of slow component of decay (τ(s)) = 147.4 ms]. Neither the rise time of the EPSC nor the time constants of decay exhibited any degree of voltage dependence over the range of -90 to +50 mV. 5. The results demonstrate that NMDA receptors on second-order vestibular neurons participate both in the direct synaptic response to primary afferent stimulation and in excitatory transmission within the intrinsic circuitry of MVN. Synaptic activation of NMDA receptors within the vestibular nuclear complex may contribute to the proposed role of NMDA receptors in vestibular compensatory mechanisms.