The synaptic activation of N-methyl-D-aspartate receptors in the rat medial vestibular nucleus

Abstract

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 gamma-aminobutyric acid receptor antagonist bicuculline (10 microM) revealed a late, slow EPSP that was blocked by the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (D-AP5; 50 microM) 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 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 microM) 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 microM) and DNQX (10 microM). 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 (tau s) = 27.6 ms, time constant of slow component of decay (tau s) = 147.4 ms].(ABSTRACT TRUNCATED AT 250 WORDS)