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Ultrastructural changes in vestibulo-ocular neurons following vestibular neurectomy in the cat.

Vestibulo-ocular (VO) neurons in the superior vestibular nucleus were labeled retrogradely with horseradish peroxidase and studied quantitatively using electron microscopy to determine the morphologic correlates of vestibular compensation. Eleven VO neurons from three normal cats were compared to 26 VO neurons in four animals killed 8 weeks after vestibular neurectomy and 13 VO cells from two animals killed 1 year after vestibular neurectomy. The results demonstrated a marked reduction (74%) in the number of synaptic profiles (SPs) on the VO cell soma in both experimental groups. Synaptic vesicles in the remaining SPs on VO neurons were fewer, smaller, and rounder than vesicles in control animals. The residual SPs also were associated with more asymmetric synapses. The experimental VO neuron showed a significant decrease in soma and organelles associated with protein synthesis.

Animals↗

Postnatal development of spike generation in rat medial vestibular nucleus neurons.

Image stability during self motion depends on the combined actions of the vestibuloocular and optokinetic reflexes (VOR and OKR, respectively). Neurons in the medial vestibular nucleus (MVN) participate in the VOR and OKR by firing in response to both head and image motion. Their intrinsic spike-generating properties enable MVN neurons to modulate firing rates linearly over a broad range of input amplitudes and frequencies such as those that occur during natural head and image motion. This study examines the postnatal development of the intrinsic spike-generating properties of rat MVN neurons with respect to maturation of peripheral vestibular and visual function. Spike generation was studied in a brain stem slice preparation by recording firing responses to current injected intracellularly through whole cell patch electrodes. MVN neurons fired spontaneously and modulated their firing rate in response to injected current at all postnatal ages. However, the input-output properties of the spike generator changed dramatically during the first two postnatal weeks. Neurons younger than postnatal day 10 could not fire faster than 80 spikes/s, modulated their firing rates over a limited range of input amplitudes, and tended to exhibit a nonlinear relationship between input current and mean evoked firing rate. In response to sustained depolarization, firing rates declined significantly in young neurons. Response gains tended to be highest in the first few postnatal days but varied widely across neurons and were not correlated with age. By about the beginning of the third postnatal week, MVN neurons could fire faster than 100 spikes/s in response to a broad range of input amplitudes, exhibited predominantly linear current-firing rate relationships, and adapted little in response to sustained depolarization. Concomitant decreases in action potential width and the time course of the afterhyperpolarization suggest that changes in potassium currents contribute to the maturation of the MVN neuronal spike generator. The results demonstrate that developmental changes in intrinsic membrane properties enable MVN neurons to fire linearly in response to a broad range of stimuli in time for the onset of visual function at the beginning of the third postnatal week.

Action Potentials↗

Ultrastructural changes in contralateral vestibulo-ocular neurons following vestibular neurectomy in the cat.

Twenty contralateral superior vestibular vestibulo-ocular neurons (SVON) from 4 cats were studied morphologically 8 weeks after a right vestibular neurectomy. Nine SVON demonstrated a 35% loss of somal synaptic profiles (SP), normal nuclear and cytoplasmic size, but a slight decrease in organelles responsible for protein synthesis (rough endoplasmic reticulum and polyribosomes). Eleven SVON showed an 82% loss of SP, decrease in cell and nuclear size, and significant reduction in rough endoplasmic reticulum (RER) and polyribosomes. These transneuronal SVON changes are presumed to be the result of commissural pathway degeneration caused by the vestibular neurectomy.

Animals↗

Effects of CGS-12066A on medial vestibular nuclear neurons.

This study aims to explore the effects of a selective 5-HT1B receptor agonist, CGS-12066A, on the neuronal excitability of the rat medial vestibular nuclear neurons. The spontaneous firing rate was decreased, and the membrane potential was hyperpolarized by CGS-12066A. The whole potassium currents were inhibited by CGS-12066A. After the calcium-dependent potassium, currents were blocked, however, CGS-12066A did not inhibit the potassium currents, suggesting that the 5-HT action site is calcium-dependent potassium currents.

Action Potentials↗

[Modulation of gamma-aminobutyric acid receptor on medial vestibular nucleus neurons in vivo].

OBJECTIVE: To investigate modulation of gamma-aminobutyric acid (GABA) and its receptors on medial vestibular nucleus neurons in vivo. METHODS: Twenty-six male Wistar rats were used. gamma-aminobutyric acid, bicuculline (BIC, gamma-aminobutyric acid A receptor antagonist) and 2-hydroxysaclofen (SAC, gamma-aminobutyric acid B receptor antagonist) were microiontophoresed on medial vestibular nucleus (MVN) neurons to determine the effects of gamma-aminobutyric acid and its antagonists on the neuronal firing rates of medial vestibular nucleus in rats in vivo. RESULTS: Microiontophoretic application of y-aminobutyric acid at 10, 30, 50 nA electric current produced inhibitory responses on 42 MVN neurons, these responses were dose-dependent decreases, firing rates (x +/- s) of MVN neurons decreased form (14.8 +/- 5.6) times/s to (8.7 +/- 3.4) times/s, (4.1 +/- 1.6) times/s and (2.2 +/- 1.1) times/s respectively; microiontophoretic application of bicuculline in 37 MVN neurons, 86.5% (32/37) neurons produced excitatory responses, 13.5% (5/37) neurons didn't response, firing rates of MVN neurons increased form (15.3 +/- 6.3) times/s to (16.8 +/- 7.1) times/s, (25.9 +/- 10.1) times/s and (32.7 +/- 11.3) times/s respectively at 10, 30, 50 nA electric current, which were dose-dependent increases, and the inhibitory responses of gamma-aminobutyric acid on MVN neurons were blocked by bicuculline completely; however, microiontophoretic application of 2-hydroxysaclofen didn't produced responses as bicuculline did. CONCLUSIONS: Modulation of gamma-aminobutyric acid on medial vestibular nucleus neurons was mediated by y-aminobutyric acid A receptor in vivo.

Animals↗

Nitric oxide modulation of the spontaneous firing of rat medial vestibular nuclear neurons.

Modulation of the spontaneous activity of rat medial vestibular nuclear neurons by nitric oxide was investigated using the whole-cell patch-clamp technique. The spike frequency was increased by sodium nitroprusside (SNP), a nitric oxide liberating agent, and it was also increased by another nitric oxide liberating agent, sodium-nitroso-N-acetylpenicillamine. L-Arginine, the substrate of nitric oxide synthase, increased the firing of the neurons. The increased SNP-induced firing was inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one (ODQ), a specific inhibitor of guanylate cyclase. These results suggest that nitric oxide increases the neuronal excitability of the neurons by a cGMP-dependent mechanism.

Action Potentials↗

Retrograde transport of [3H]-D-aspartate label by cochlear and vestibular efferent neurons.

[3H]-D-aspartic acid was injected into the inner ear of rats. After a six hour survival time, labeled cells were found at all locations known to contain efferent cochlear or vestibular neurons. Most labeled neurons were found in the ipsilateral lateral superior olivary nucleus (LSO), although both ventral nuclei of the trapezoid body (VTB), group E, and the caudal pontine reticular nucleus (CPR) just adjacent to the ascending limb of the facial nerve also contained labeled cells. Because not all efferent neurons in the rat could be previously shown to be cholinergic, aspartate and glutamate are efferent transmitter candidates.

Animals↗

Voltage-gated calcium channels contribute to the pattern of the resting discharge in guinea pig medial vestibular nucleus neurons.

In brainstem slices of guinea pigs perfused with artificial cerebro-spinal fluid (ACSF), the discharge of all the spontaneously active neurons of the medial vestibular nucleus (MVN) is regular. It has been reported that prolonged exposure to a low Ca(2+) medium could induce these neurons to fire bursts of spikes. In this study, we performed a systematic exploration of the spontaneous activity of the guinea pig MVN neurons by extracellular recordings in slices perfused either with a low Ca(2+)-high Mg(2+) medium, or with ACSF added with omega-agatoxin-IVA and with omega-conotoxin-GVIA. The percentage of recorded neurons which fired bursts, was 67% in low Ca(2+)-high Mg(2+) medium and 34% under the action of Ca(2+) channel blockers. These results show that the sensitivity of the firing properties to divalent cations is not shared by all of the MVN neurons and that the regularity of firing of a class of MVN neurons depends on the Ca(2+) channels they express in their membranes.

Action Potentials↗

Spontaneous synaptic activity is primarily GABAergic in vestibular nucleus neurons of the chick embryo.

The principal cells of the chick tangential nucleus are vestibular nucleus neurons participating in the vestibular reflexes. In 16-day embryos, the application of glutamate receptor antagonists abolished the postsynaptic responses generated on vestibular-nerve stimulation, but spontaneous synaptic activity was largely unaffected. Here, spontaneous synaptic activity was characterized in principal cells from brain slices at E16 using whole cell voltage-clamp recordings. With KCl electrodes, the frequency of spontaneous inward currents was 3.1 Hz at -60 mV, and the reversal potential was +4 mV. Cs-gluconate pipette solution allowed the discrimination of glycine/GABA(A) versus glutamate receptor-mediated events according to their different reversal potentials. The ratio for spontaneous excitatory to inhibitory events was about 1:4. Seventy-four percent of the outward events were GABA(A), whereas 26% were glycine receptor-mediated events. Both pre- and postsynaptic GABA(B) receptor effects were shown, with presynaptic GABA(B) receptors inhibiting 40% of spontaneous excitatory postsynaptic currents (sEPSCs) and 53% of spontaneous inhibitory postsynaptic currents (sIPSCs). With TTX, the frequency decreased approximately 50% for EPSCs and 23% for IPSCs. These data indicate that the spontaneous synaptic activity recorded in the principal cells at E16 is primarily inhibitory, action potential-independent, and based on the activation of GABA(A) receptors that can be modulated by presynaptic GABA(B) receptors.

Animals↗

Potent effects of a selective cannabinoid receptor agonist on some guinea pig medial vestibular nucleus neurons.

Binding studies have indicated that the density of the cannabinoid CB, receptor is very low in the vestibular nucleus complex compared to other areas of the central nervous system (CNS), suggesting that CB1 receptors may have little functional significance for the vestibular nucleus. However, the dizziness often produced by cannabis suggests that the vestibular system may be implicated. We investigated the effects of the selective CB1 receptor agonist, CP 55940 (the levorotatory enantiomer of desacetyllevonantradol), on medial vestibular nucleus neurons in guinea pig brainstem slices in vitro. Only 3/18 medial vestibular nucleus neurons tested with 1 microM CP 55940 showed changes in firing rate, however these were decreases with an average magnitude of 72.3%; 3/4 neurons tested with 10 microM CP 55940 showed decreases with an average magnitude of 92.7% (P < 0.05 in both cases). In all cases the effects of CP 55940 were long-lasting. These results suggest that despite the low density of CB1 receptors in the vestibular nucleus complex, they may be of functional significance for the behavioural effects of cannabis use.

Animals↗

Cross-striolar and commissural inhibition in the otolith system.

Neural connections from the saccular and utricular nerves to the ipsilateral vestibular neurons and the commissural effects were studied by using intracellular recordings of excitatory (E) and inhibitory (I) postsynaptic potentials (PSPs) in vestibular neurons of cats after focal stimulation of the saccular and the utricular maculae. Neural circuits from the maculae to vestibular neurons, termed cross-striolar inhibition, may provide a mechanism for increasing the sensitivity to linear acceleration and tilt of the head. It was examined whether secondary vestibular neurons activated by an ipsilateral otolith organ received a commissural inhibition from a contralateral otolith organ that occupied the same geometric plane. Results suggest that utricular-activated vestibular neurons receiving commissural inhibition may provide a mechanism for increasing the sensitivity to horizontal linear acceleration and tilt of the head. The commissural inhibition of the saccular system was much weaker than that of the utricular system.

Afferent Pathways↗

[Effects of ifenprodil on lateral vestibular nucleus neurons in the cat (author's transl)].

Electrophysiological studies were performed to elucidate effects of ifenprodil, an antivertigo drug, on neuron activity in the lateral vestibular nucleus (LVN) of cats anesthetized with alpha-chloralose. LVN neurons were classified into three types, according to the response pattern upon vestibular nerve stimulation: monosynaptic, polysynaptic I and polysynaptic II neurons, which fired spikes with the mean latencies of 1.07 +/- 0.12 (n = 6), 2.20 +/- 0.19 (n = 8) and 16.37 +/- 2.11 msec (n = 7), respectively. Intravenous administration of ifenprodil up to 5 mg/kg did not affect spike generation of monosynaptic neurons. Spike generation of polysynaptic I and II neurons was dose-dependently inhibited by ifenprodil up to 1 mg/kg. However, increasing doses of the drug up to 5 and 10 mg/kg produced complex effects such as an enhancement of the inhibitory effect in some neurons or a facilitation of responses in others. These results indicate that ifenprodil acts on the polysynaptic I and II neurons without affecting the monosynaptic neurons. It is likely that a small dose of ifenprodil may directly inhibit polysynaptic neurons and higher doses may indirectly enhance the responsiveness of the neurons, probably as a result of an increase in blood flow in the vertebral artery.

Adrenergic alpha-Antagonists↗

Hyperpolarization-activated (Ih) current in mouse vestibular primary neurons.

The presence of a hyperpolarization-activated inward current (Ih) was investigated in mouse vestibular primary neurons using the whole-cell patch-clamp technique. In current-clamp configuration, injection of hyperpolarizing currents induced variations of membrane voltage with prominent time-dependent rectification increasing with current amplitudes. This effect was abolished by 2 mM Cs+ or 100 microM ZD7288. In voltage-clamp configuration, hyperpolarization pulses from -60 mV to -140 mV triggered a slow activating and non inactivating inward current that was sensitive to the two blockers, but insensitive to 5 mM Ba2+. Changing Na+ and K+ concentrations demonstrated that Ih current is carried by both these monovalent cations. This is the first demonstration of a Ih current in vestibular primary neurons.

Animals↗

Effect of epidural spinal cord stimulation on the activity of lateral vestibular nucleus neurons in the cat.

The activity of neurons in Deiters' lateral vestibular nucleus was recorded in decerebrate cats before, during and after spinal cord stimulation. An almost equal number of units were inhibited and excited early during stimulation. Later during stimulation the majority of units was inhibited. Early after cessation of stimulation an ever larger number of units were inhibited to an even larger extent (for about 2 imp/s on the average). Later after stimulus cessation the predominant inhibitory effect could still be noted, as well as excitation in some units. The results could support the hypothesis that the inhibition of Deiters' neurons during and for some time after epidural cord stimulation may play a part in the decrease of limb spasticity. The mechanism of inhibitory and excitatory unitary responses, side effects during stimulation and differences between the experimental model and human state are discussed.

Animals↗

Ethanol reduces spontaneous firing and potentiates GABA-induced currents in acutely dissociated rat medial vestibular nucleus neurons.

Effects of ethanol on acutely dissociated medial vestibular nucleus (MVN) neurons were examined using whole-cell patch clamp technique to elucidate the mechanism underling the inhibitory effects of this drug on the neurons observed in in vivo studies. Dissociated MVN neurons obtained from male Wistar rats were superfused with extracellular solution continuously at a flow rate of 1-3 ml/min. Whole-cell patch clamp recording was performed according to standard procedures. GABA was applied by pressure from a pipette placed near the neuron recorded. Ethanol was applied via pipette by pressure or through bath perfusion. Acutely dissociated MVN neurons regularly showed spontaneous firing. Under current-clamp conditions, bath application of ethanol at 0.1% caused hyperpolarization and reduced spontaneous firing in MVN neurons, while 0.1% ethanol did not affect spontaneous firing. Pulse application of higher concentrations of ethanol (0.1-1%) caused similar hyperpolarization. Under voltage-clamp conditions at a holding potential of -30 mV, GABA induced outward currents in a concentration-dependent manner. GABA-induced currents were potentiated in the presence of 0.01% ethanol. These results indicate that high concentrations of ethanol (0.1-1%) directly induce inhibition of spontaneous firing and low concentrations (0.01%) enhance GABA-induced inhibition in the MVN neurons.

Action Potentials↗

Responses of nucleus reticularis tegmenti pontis neurons to vestibular stimulation in the rat.

Forty-nine neurons were recorded in the nucleus reticularis tegmenti pontis (NRTP) during horizontal vestibular and/or optokinetic stimulation in immobilized pigmented rats. During optokinetic stimulation, the response of NRTP neurons was either unidirectional (51%) or bidirectional (49%). Histological reconstruction showed that unidirectional neurons were located in the dorsal-medial part of NRTP, and bidirectional neurons in the lateral part. All neurons exhibited a response during pure vestibular sinusoidal stimulation in the frequency range 0.025 Hz-0.2 Hz. NRTP neurons were divided into two groups according to their threshold to vestibular stimulation. Group A neurons had a low threshold, a low spontaneous activity and their firing frequency slowly increased with acceleration. Group B neurons showed opposite characteristics. Phase and gain analysis suggested that NRTP neurons carry a head velocity signal. After hemiflocculectomy, the gain of the vestibular response of contralateral NRTP neurons increased. From these data, the role of NRTP in the horizontal vestibulo-oculomotor is discussed.

Action Potentials↗

Tonic activity and GABA responsiveness of medial vestibular nucleus neurons in aged rats.

The tonic discharge of rat medial vestibular nucleus (MVN) neurons, and their responsiveness to GABA receptor agonists were investigated in slices prepared from aged rats (24 months old). Aged MVN neurons showed regular spontaneous activity similar to that seen in slices from young adults. However the inhibitory effects of the GABA(A) agonist muscimol on the spontaneous activity of aged MVN neurons were significantly greater than in young MVN neurons. Inhibitory responses to the GABA(B) agonist baclofen also tended to be greater in slices from aged animals, but this difference was not statistically significant. The regular discharge of aged MVN neurons at firing rates similar to those in young animals suggests that the intrinsic excitability of MVN cells is maintained with age. The up-regulation of GABA(A) receptor efficacy in aged MVN neurons may compensate for changes in inhibitory inputs from vestibular commissures and cerebellum that may occur with neuronal loss in the aged brain.

Aging↗