UNCROSSED DISYNAPTIC INHIBITION OF 2ND-ORDER VESTIBULAR NEURONS AND ITS INTERACTION WITH MONOSYNAPTIC EXCITATION FROM VESTIBULAR NERVE AFFERENT-FIBERS IN THE FROG
H. Straka et N. Dieringer, UNCROSSED DISYNAPTIC INHIBITION OF 2ND-ORDER VESTIBULAR NEURONS AND ITS INTERACTION WITH MONOSYNAPTIC EXCITATION FROM VESTIBULAR NERVE AFFERENT-FIBERS IN THE FROG, Journal of neurophysiology, 76(5), 1996, pp. 3087-3101
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.