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PubMed1991

Enkephalin mRNA production by cochlear and vestibular efferent neurons in the gerbil brainstem.

Preproenkephalin mRNA production by efferent neurons projecting to the gerbil inner ear was assessed using combined in situ hybridization and retrograde labeling with fluorescent tracers. Virtually all vestibular efferent neurons were positive for preproenkephalin mRNA. Of the cochlear efferents, one-half of the medial olivocochlear neurons were positive for enkephalin. All lateral olivocochlear neurons were negative for enkephalin. The results suggest that there are two, biochemically distinct subpopulations of medial olivocochlear efferents in the gerbil.

Animals↗
PubMed2001

Primary neurotransmitters and regulatory substances onto vestibular nucleus neurons.

This review article focused on the primary neurotransmitters involved in transmission from the otolith to the vestibular nucleus (VN), especially in relation to the neurotransmission to the VN neurons (gravity-sensitive neurons) activated by tilt stimulation. The medial vestibular nucleus (MVN) neurons were classified in 8 types (alpha-theta) according to the patterns in response to the clockwise and counterclockwise tilt-stimulations. The tilt-induced firing was inhibited by GDEE (a non-selective glutamate receptor antagonist) and/or atropine (a muscarinic receptor antagonist). Thus, glutamate and/or acetylcholine may serve as the primary neurotransmitters. This conclusion is supported by the previous findings that glutamate exists in the vestibular nerve and is released from the nerve besides the presence of glutamate receptor subtypes in the VN. In addition, acetylcholine induced atropine-reversible firing of MVN neurons, and the enzymes involved in acetylcholine synthesis/metabolism are also found in the VN. Furthermore, serotonin was found to inhibit the MVN neuronal activities via the 5-HT1A receptors. As such, the 5-HT1A agonist, tandospirone, may be effective in preventing and/or treating motion sickness and/or space sickness.

Acetylcholine↗
PubMed1984

Spatial and temporal response properties of secondary neurons that receive convergent input in vestibular nuclei of alert cats.

Responses to rotation in many vertical and horizontal planes were studied in electrically identified secondary vestibular neurons of alert cats. This report concerns secondary neurons that gave responses which could not be explained as due to a summation of semicircular canal inputs. These cells responded to sinusoidal rotation of the cat in any vertical plane, and response phase depended on the plane of rotation. The responses were modeled as the result of summation of two inputs that differed in their spatial orientations and dynamics. Response dynamics and a comparison of responses to vertical and horizontal rotations showed that some cells were sensitive to rotation with respect to gravity. Their responses both to gravity and horizontal rotations argue that these secondary neurons received convergent otolith and canal inputs. Some cells also had oculomotor related discharges and/or responded weakly to neck rotation.

Animals↗
PubMed1993

Excitatory and inhibitory effects of 5-hydroxytryptamine on the firing rate of medial vestibular nucleus neurons in the rat.

The effects of microiontophoretic application of 5-hydroxytryptamine (5-HT) on the neuronal firing rate of the medial vestibular nucleus (MVN) were studied in anaesthetized rats. Ninety-three % of the units modified their background activity following 5-HT iontophoresis, enhancements of the firing rate being recorded in 42%, decreases in 38% and biphasic effects in 13%. 5-HT antagonists methysergide and ketanserin blocked the excitatory but not the inhibitory responses to 5-HT. These latter were, however, mimicked by 5-HT agonists 5-methoxy-N,N-dimethyltryptamine (5MeODMT) and 8-hydroxy-2(di-n-propyl-amino)tetralin (8-OH-DPAT). It is concluded that 5-HT can variously influence the background activity of MVN neurons and that 5-HT2 and probably 5-HT1A receptors are involved in the responses.

Action Potentials↗
PubMed1995

Properties of otolith-related vestibular nuclear neurons in response to bidirectional off-vertical axis rotation of the rat.

In decerebrate rats, the responses of tilt-sensitive neurons in the lateral and descending vestibular nuclei were studied during constant velocity 10 degrees off-vertical axis rotations (OVAR) in the clockwise (VW) and counterclockwise (CCW) directions. Seventy three otolith-related units showed a sinusoidal position-dependent discharge modulation to OVAR of both directions; 20 of these showed clipped firing rates in parts of a 360 degree OVAR cycle. With increase in the velocity of rotation (1.75-15 degrees/s), one group of units (n = 36) showed a stable ratio of bidirectional response sensitivity and symmetric response magnitudes to CW and CCW rotations. These units showed gain tuning ratios similar to those of narrowly spatiotemporal-tuned neurons. The other group of OVAR responsive units (n = 13) exhibited velocity-variable and asymmetric bidirectional response sensitivities. Their gain tuning ratios were similar to those of broadly spatiotemporal-tuned neurons. For units with velocity-stable and symmetric bidirectional response sensitivity as well as gain tuning ratio of the narrowly spatiotemporal-tuned neurons, their response gains remained stable with velocity. Some showed stable response phase lead or lag with velocity increase while others showed progressive shifts from response lead of 13 degrees to response lag of -25 degrees. The best response orientations of these units with velocity-stable and symmetric bidirectional response sensitivity were found to point in all directions on the place of rotation. The functional significance of these tilt- and OVAR-sensitive central otolith neurons is discussed.

Animals↗
PubMed1992

Comparison of the effects of NMDA antagonists on medial vestibular nucleus neurons in brainstem slices from labyrinthine-intact and chronically labyrinthectomized guinea pigs.

The responses of ipsilateral medial vestibular nucleus (MVN) neurons in brainstem slices from guinea pigs compensated for a unilateral labyrinthectomy (UL), to the N-methyl-D-asparate (NMDA) receptor/channel antagonists CPP and MK801, were compared with those of MVN neurons in brainstem slices from labyrinthine-intact guinea pigs observed in a previous study. The average resting activity of ipsilateral MVN neurons from compensated animals was significantly higher than that for MVN neurons from labyrinthine-intact animals; however, there were no significant differences in the average magnitude of the decrease in firing rate from baseline in response to CPP or MK801 and the only significant difference in the number of responses was to MK801, where fewer ipsilateral MVN neurons from compensated animals responded with a decrease in firing rate. These results suggest that vestibular compensation is not associated with an up-regulation or increased affinity of NMDA receptors in the MVN ipsilateral to the UL.

Animals↗
PubMed1998

Effects of toluene on tonic firing and membrane properties of rat medial vestibular nucleus neurones in vitro.

The effects of toluene on discharge rate and membrane properties of tonically active medial vestibular nucleus (MVN) neurones were investigated in an in vitro slice preparation of the dorsal brainstem of the rat. The majority of the cells (50/56) were inhibited in a dose-dependent manner by toluene. The inhibitory effects of toluene persisted after blockade of synaptic transmission. Complementary patch-clamp recordings showed that toluene caused a hyperpolarisation of 2-5 mV associated with an increase in membrane conductance. These findings indicate that toluene might interfere with specific ion channels or the receptors regulating them along the cell membrane. The effective toluene concentrations used in this experiment are comparable to the concentrations producing vestibulo-ocular disturbances in vivo.

Action Potentials↗
PubMed1989

Ethanol potentiates the effect of gamma-aminobutyric acid on medial vestibular nucleus neurons responding to horizontal rotation.

Electrophysiological studies were performed to determine whether or not ethanol potentiates the inhibitory effects of gamma-aminobutyric acid (GABA) on medial vestibular nucleus (MVN) neurons responding to horizontal sinusoidal rotation using alpha-chloralose anesthetized cats. The MVN neurons were classified into types I, II, III and IV neurons according to the responses to the horizontal rotation of the animal placed on the turntable in directions ipsilateral and contralateral to the recording site. In addition, the effects of ethanol and GABA on type I neurons were also examined. Micro-osmotic application of ethanol up to 100 nA did not affect the spontaneous firing or the rotation-induced increase in firing of type I neurons. However, the inhibitory effects of GABA up to 50 nA on the rotation-induced increase in firing were potentiated during simultaneous application of ethanol up to 100 nA. This potentiated inhibition was blocked by iontophoretic application of bicuculline (25-150 nA) and picrotoxin (45-150 nA). These results suggest that ethanol potentiates the inhibitory effects of GABA on MVN type I neurons by acting on the GABA receptor and/or receptor-coupled chloride ion channel.

Animals↗
PubMed2003

Melatonin inhibits rat medial vestibular nucleus neuron activity in vitro.

The present study evaluated the effects of melatonin on the discharge rate of tonically active medial vestibular nucleus (MVN) neurons in an in vitro slice preparation of the rat dorsal brainstem. The results demonstrated that, when melatonin was applied to the slice for a period of 7-10 min, a decrease in MVN neuron firing rate was observed in 21/58 (36%) of the cells sampled. The inhibitory effects of melatonin were present in synaptic uncoupling condition and were mimicked by 2-iodomelatonin, a non-selective agonist with high affinity for melatonin membrane receptor subtypes (MT(1), MT(2), MT(3)). The MT(2) receptor antagonists luzindole and 4-phenyl-2-propionamidotetraline and the MT(3) receptor antagonist prazosin did not, however, antagonise the inhibitory effects of melatonin, indicating that melatonin may act on MVN neurons through an MT(1) receptor-mediated mechanism.

Action Potentials↗
PubMed1995

Cellular processing of temporal information in medial vestibular nucleus neurons.

Quantitative descriptions of the cellular transformations from behaviorally relevant inputs into temporal patterns of firing are crucial for understanding information processing in systems of neurons and for incorporating biological properties of neurons into models of the neural control of behavior. To understand how neurons that mediate vestibulo-ocular behavior transform their inputs into temporal patterns of firing, we examined responses of medial vestibular nucleus (MVN) neurons to current injected intracellularly. MVN neurons recorded from avian brain slices fired spontaneously. Sinusoidal modulation of input current produced precisely sinusoidal modulation of firing rate. The transformation between input current and firing rate was remarkably linear: firing rate scaled linearly as a function of current amplitude, and the responses to steps of input current were predicted accurately from the linear superposition of responses to sinusoidal modulation of input current. Over the physiological range of head movement frequencies, from 0.1 to 10 Hz, peak-to-peak modulation of firing rate was relatively constant or increased slightly in most neurons. In contrast, when hyperpolarizing current was used to keep neurons below threshold for action potentials, the frequency response of the membrane potential behaved like a low-pass filter. These results imply that the membrane conductances that are active when MVN neurons fire compensate for the low-pass characteristics of the membrane to allow faithful transmission of high frequency head movement signals.

Animals↗
PubMed1998

The neurosteroid pregnenolone sulfate excites medial vestibular nucleus neurons.

To examine the relationship between neurosteroids and vertigo we performed electrophysiological studies to determine whether pregnenolone sulfate (PS) affects the activity of medial vestibular nucleus (MVN) neurons in alpha-chloralose-anesthetized cats. Single neuronal activities in the MVN were recorded extracellularly using a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette. 3 mM PS, 1 M glutamate and 3 mM NaCl were applied microiontophoretically in the immediate vicinity of the target neurons. The effects of these drugs were then examined on type I and type II neurons, identified by their responses to horizontal and sinusoidal rotations. The iontophoretic application of PS dose-dependently increased the spontaneous firing of both type I and type II neurons. The larger increase in firing was observed in type I neurons as compared with type II neurons following the PS application. These results suggest that PS excites types I and II neurons differentially, presumably resulting in a disturbance of harmony of the vestibulo-ocular reflex with ensuing development of vertigo.

Animals↗
PubMed1995

Morphologic changes in superior vestibulo-ocular neurons and vestibular nerve following labyrinthectomy in the cat.

Morphologic changes in ipsilateral superior vestibulo-ocular neurons (SVON) and the vestibular nerve were measured in 4 cats 8 weeks after labyrinthectomy and 4 cats 1 year after labyrinthectomy. There is a 20% decrease in SVON size and 30% decrease in rough endoplasmic reticulum and ribosomes with no change in the volume fractions of Golgi apparatus or mitochondria. In the central nervous system degeneration of the vestibular nerve terminals ipsilateral to the labyrinthectomy was represented by a 25% loss of synaptic profiles (SP) on SVON at 8 weeks and 57% loss of SP at 1 year after labyrinthectomy. There was no significant loss of fiber number in the vestibular nerve at 8 weeks post lesion but a 35% loss of fibers primarily of the large size at 1 year post lesion.

Animals↗
PubMed1998

Vestibular ganglion neurons survive the loss of their cerebellar targets.

Neuronal survival during mammalian development crucially depends on target-derived neurotrophic factors. Target loss removes this trophic support and leads in most cases to the transsynaptic retrograde degeneration of the respective afferents. Primary vestibular afferents (PVA) originating from bipolar neurons in the vestibular ganglion (VG) are the first mossy fibers that enter the cerebellum, but little is known about the survival requirements of VG neurons. In the present study the influence of the differential granule cell (GC) target loss on the survival of VG neurons was studied quantitatively using unbiased stereological methods in the cerebellar mutants Purkinje cell degeneration (pcd/pcd), Lurcher (Lc/+), and Weaver (wv/wv). Neither the secondary GC loss in the Purkinje cell deficient mutants pcd/pcd and Lc/+, nor the primary loss of GCs in wv/wv produced any significant reduction in the total number of bipolar neurons in the VG compared to controls. So, PVA neurons are highly resistant to cerebellar target deprivation and survive in the absence of cerebellar granule and Purkinje cells, regardless of whether the target loss occurs before (in wv/wv), during (in Lc/+) or after (in pcd/pcd) the mossy fiber-granule cell synaptogenesis.

Animals↗
PubMed2005

Decreases in CaMKII activity trigger persistent potentiation of intrinsic excitability in spontaneously firing vestibular nucleus neurons.

Calcium/calmodulin-dependent protein kinase II (CaMKII) has been described as a biochemical switch that is turned on by increases in intracellular calcium to mediate synaptic plasticity. Here, we show that reductions in CaMKII activity trigger persistent increases in intrinsic excitability. In spontaneously firing vestibular nucleus neurons, CaMKII activity is near maximal, and blockade of CaMKII activity increases excitability by reducing BK-type calcium-activated potassium currents. Firing rate potentiation, a form of plasticity in which synaptic inhibition induces long-lasting increases in excitability, is occluded by prior blockade of CaMKII and blocked by addition of constitutively active CaMKII. Reductions in CaMKII activity are necessary and sufficient to induce firing rate potentiation and may contribute to motor learning in the vestibulo-ocular reflex.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

[Vestibular neuritis].

Vestibular neuronitis is an acute disorder of the vestibular apparatus which manifests by sudden vertigo, without apparent cause, and without auditory or neurological symptoms. Clinically and by thermal stimulation tests, it is characterised by unilateral peripheral vestibular deficit. Evolution is favourable in several days to several weeks and prognosis is favourable, although disorders of moderate intensity may rather often persist, in the form of positional vertigo, sometimes paroxysmal, or disorders of equilibrium on abrupt movement. Careful history-taking and clinical examination, routine evaluation of the vestibular-cochlear apparatus and follow-up of the patient during the first days can eliminate the possibility of vascular cerebellar syndrome, which would require emergency imaging and possibly recuperation by surgery. The aetiology of vestibular neuronitis remains mysterious: inflammatory, viral, vascular? Sedatives acting on the vestibular system should be given for only a very limited time; they inhibit the mechanism of central compensation, which is on the contrary favoured by early vestibular function and rehabilitation.

Acute Disease↗
PubMed1995

Further evidence on the contribution of GABAA receptors to the GABA-mediated inhibition of medial vestibular nucleus neurones in vitro.

The present study investigated the electrophysiological effects of the selective and potent GABAA receptor agonist, isoguvacine, on guinea-pig medial vestibular nucleus (MVN) neurones in brainstem slices. The results confirm that many MVN neurones have GABAA receptors and that, even at concentrations as low as 10(-8) M, GABA is capable of exerting a powerful inhibitory effect on these neurones via GABAA receptors. The finding that > 50% of neurones did not respond to isoguvacine, even at concentrations of 10(-6) M, suggested that only a specific subset of MVN neurones have GABAA receptors. Since many type I MVN neurones are believed to have postsynaptic GABAA receptors, it is possible that selective agonists such as isoguvacine may be useful in identifying type I neurones in vitro.

Action Potentials↗
PubMed2006

Inhibitory synaptic transmission differs in mouse type A and B medial vestibular nucleus neurons in vitro.

Fast inhibitory synaptic transmission in the medial vestibular nucleus (MVN) is mediated by GABA(A) receptors (GABA(A)Rs) and glycine receptors (GlyRs). To assess their relative contribution to inhibition in the MVN, we recorded miniature inhibitory postsynaptic currents (mIPSCs) in physiologically characterized type A and type B MVN neurons. Transverse brain stem slices were prepared from mice (3-8 wk old), and whole cell patch-clamp recordings were obtained from visualized MVN neurons (CsCl internal; Vm = -70 mV; 23 degrees C). In 81 MVN neurons, 69% received exclusively GABA(A)ergic inputs, 6% exclusively glycinergic inputs, and 25% received both types of mIPSCs. The mean amplitude of GABA(A)R-mediated mIPSCs was smaller than those mediated by GlyRs (22.6 +/- 1.8 vs. 35.3 +/- 5.3 pA). The rise time and decay time constants of GABA(A)R- versus GlyR-mediated mIPSCs were slower (1.3 +/- 0.1 vs. 0.9 +/- 0.1 ms and 10.5 +/- 0.3 vs. 4.7 +/- 0.3 ms, respectively). Comparison of type A (n = 20) and type B (n = 32) neurons showed that type A neurons received almost exclusively GABA(A)ergic inhibitory inputs, whereas type B neurons received GABA(A)ergic inputs, glycinergic inputs, or both. Intracellular labeling in a subset of MVN neurons showed that morphology was not related to a MVN neuron's inhibitory profile (n = 15), or whether it was classified as type A or B (n = 29). Together, these findings indicate that both GABA and glycine contribute to inhibitory synaptic processing in MVN neurons, although GABA dominates and there is a difference in the distribution of GABA(A) and Gly receptors between type A and type B MVN neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗