UNCROSSED DISYNAPTIC INHIBITION OF 2ND-ORDER VESTIBULAR NEURONS AND ITS INTERACTION WITH MONOSYNAPTIC EXCITATION FROM VESTIBULAR NERVE AFFERENT-FIBERS IN THE FROG

1. Eighth nerve evoked responses in central vestibular neurons (n = 14 6) were studied in the isolated brain stem of frogs. Ninety percent of these neurons responded with a monosynaptic excitatory postsynaptic p otential (EPSP) after electrical stimulation of the ipsilateral VIIIth nerve. In 5% of these neurons, the EPSP was truncated by a disynaptic inhibitory postsynaptic potential (IPSP), and in 5% of these neurons a pure disynaptic IPSP was evoked. 2. Disynaptic IPSPs superimposed up on apparently pure EPSPs were revealed by bath application of the glyc ine receptor antagonist strychnine (0.5-5 mu M) or of the gamma-aminob utyric acid-A (GABA(A)) receptor antagonist bicuculline (0.5-2 mu M). The evoked EPSP increased in most central vestibular neurons (strychni ne: 15 out of 16 neurons; bicuculline 26 out of 29 neurons). At higher stimulus intensities, the evoked spike discharge increased from 2 to 3 spikes before up to 8-10 spikes per electrical pulse during the appl ication of blocking agents. The unmasked disynaptic inhibitory compone nt increased with stimulus intensity to a different extent in differen t neurons. 3. Lesion studies demonstrated that these inhibitory compon ents were generated ipsilaterally with respect to the recording side. The disynaptic strychnine-sensitive inhibition was mediated by neurons located either in the ventral vestibular nuclear complex (VNC) or in the adjacent reticular formation. The spatial distribution of the disy naptic inhibition was investigated by simultaneous recordings of VIIIt h nerve-evoked field potentials at different rostrocaudal locations of the VNC. A significant strychnine-sensitive component was detected in the middle and caudal parts but not in the rostral part of the VNC. A bicuculline-sensitive component was detected in the rostral and in th e caudal parts but not in the middle part of the VNC. In view of a sim ilar rostrocaudal distribution of glycine- or GABA-immunoreactive neur ons in the VNC of frogs, our results suggest that part of the disynapt ic inhibition is mediated by local interneurons with a spatially restr icted projection area. 4. The monosynaptic EPSP of second-order vestib ular neurons was mediated in part by N-methyl-D-aspartate (NMDA) and i n part by non-NMDA receptors. The relative contribution of the NMDA re ceptor-mediated component of the EPSP decreased with stronger stimuli. This negative correlation could have resulted from a preferential act ivation of NMDA receptors via thick vestibular nerve afferent fibers. Alternatively, the activation of NMDA receptors became disfacilitated at higher stimulus intensities due to the recruitment of disynaptic in hibitory inputs. Comparison of data obtained in the presence and in th e absence of these glycine and GABA(A) receptor blockers indicates a p referential activation of NMDA receptors via larger-diameter vestibula r nerve afferent fibers. 5. The kinetics of NMDA receptors (delay, ris e time) activated by afferent nerve inputs were relatively fast. These fast kinetics were independent of superimposed IPSPs. The association of these receptors with large-diameter vestibular nerve afferent fibe rs suggests that fast NMDA receptor kinetics might be matched to the m ore phasic response dynamics of the large diameter vestibular afferent neurons to natural head accelerations.