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Labyrinthectomy changes T-type calcium channels in vestibular neurones of the guinea pig.

In the vestibular nuclei of the awake guinea pig, all neurones are spontaneously active. After unilateral labyrinthectomy, this activity virtually disappears on the ipsilateral side, but is completely restored one week later. In a recent study, we observed that the restoration of spontaneous activity was correlated with an increase in pacemaker activity. In the current study, we found that the ratio of medial vestibular nucleus (MVN) neurones endowed with one of the currents known to play a role in pacemaker activity (i.e. low-threshold calcium current; LTCC) increased from 29% in control guinea pigs to 65% in animals labyrinthectomised on the ipsilateral side one week earlier. Yet this change was not correlated with a modification of the ratio of neurones expressing any of the three related protein-channels (alpha1G, alpha1H and alpha1I).

Action Potentials↗

Linear spatio-temporal convergence in vestibular neurons of the primate nucleus fastigii.

Vestibular responses in the primate fastigial nucleus (FN) do often not follow the simple cosine tuning observed in primary vestibular afferents. The present report demonstrates that these more complex patterns can mostly be attributed to simple linear summation of spatially and temporally diverse cosine-tuned input signals (linear spatio-temporal convergence, STC). Analyses following from this elementary finding, however, reveal frequency-dependent properties in many FN neurons, which are difficult to reconcile with existing concepts of possible functions of STC in central vestibular areas. The demonstration that STC linearity holds for FN responses is thus of both theoretical and practical relevance, allowing shortening of future experimental protocols and facilitating comparison of the observed spatio-temporal response dynamics with those at other stages of vestibular signal processing.

Action Potentials↗

Three types of depolarization-activated potassium currents in acutely isolated mouse vestibular neurons.

The nature and electrophysiological properties of Ca(2+)-independent depolarization-activated potassium currents were investigated in vestibular primary neurons acutely isolated from postnatal mice using the whole cell configuration of the patch-clamp technique. Three types of currents were identified. The first current, sensitive to TEA (I(TEA)) and insensitive to 4-aminopyridine (4-AP), activated at -40 mV and exhibited slow activation (tau(ac), 38.4 +/- 7.8 ms at -30 mV, mean +/- SD). I(TEA) had a half activation potential [V(ac(1/2))] of -14.5 +/- 2.6 mV and was inactivated by up to 84.5 +/- 5.7% by 10-s conditioning prepulses with a half inactivation potential [V(inac(1/2))] of -62.4 +/- 0.2 mV. The second current, sensitive to 4-AP (maximum block around 0.5 mM) and to alpha-dendrotoxin (I(DTX)) appeared at -60 mV. Complete block of I(DTX) was achieved using either 20 nM alpha-DTX or 50 nM margatoxin. This current activated 10 times faster than I(TEA) (tau(ac), 3.5 +/- 0.8 ms at -50 mV) with V(ac(1/2)) of -51.2 +/- 0.6 mV, and inactivated only slightly compared with I(TEA) (maximum inactivation, 19.7 +/- 3.2%). The third current, also sensitive to 4-AP (maximum block at 2 mM), was selectively blocked by application of blood depressing substance (BDS-I; maximum block at 250 nM). The BDS-I-sensitive current (I(BDS-I)) activated around -60 mV. It displayed fast activation (tau(ac), 2.3 +/- 0.4 ms at -50 mV) and fast and complete voltage-dependent inactivation. I(BDS-I) had a V(ac(1/2)) of -31.3 +/- 0.4 mV and V(inac(1/2)) of -65.8 +/- 0.3 mV. It displayed faster time-dependent inactivation and recovery from inactivation than I(TEA). The three types of current were found in all the neurons investigated. Although I(TEA) was the major current, the proportion of I(DTX) and I(BDS-I) varied considerably between neurons. The ratio of the density of I(BDS-I) to that of I(DTX) ranged from 0.02 to 2.90 without correlation with the cell capacitances. In conclusion, vestibular primary neurons differ by the proportion rather than the type of the depolarization-activated potassium currents they express.

4-Aminopyridine↗

Medial vestibular neurons are endogenous pacemakers whose discharge is modulated by neurotransmitters.

1. Neurons in the medial vestibular nucleus (MVN), recorded in a rat brain slice preparation, exhibit a highly regular, high-frequency (5- to 35-Hz) spontaneous discharge. The rhythmic firing rate was constant (< 5% variation) and sustained for a long time (maximum observation, 4 hr). 2. The rhythmic firing was evident even in neurons (n = 15) completely isolated from exogenous input fibers, suggesting that it is due to an endogenous pacemaker property. When recorded intracellularly, the discharge was found to be associated with a smooth, concave pacemaker prepotential, and the rate of firing was reduced in proportion to applied hyperpolarizing current, indicating that these are pacemaker discharges. 3. This conclusion is supported by the observation that perfusion with a low-calcium/high-magnesium Krebs-Ringer solution, which completely and reversibly blocks all synaptic transmission, did not abolish the spontaneous discharge. The low-calcium/high-magnesium solution increased spontaneous firing in some neurons and decreased in others, suggesting that the firing is synaptically modulated and the synaptic influence is tonically active. 4. Application of kynurenate (10 mM), an antagonist of the excitatory amino acid receptors, gradually reduced neuronal discharges in most neurons (22 of 25), while the addition of 10 mM sucrose as an osmotic control had no effect. Depression of neuronal discharges reached its minimum (an average of 60% of the control level) and was maintained at that level until gradually washed out. The rhythmic firing pattern persisted in all neurons even after the excitatory receptors were blocked. 5. When the GABAA receptor antagonist, bicuculline (20 microM), was applied, elevation of neuronal discharges was evident in most neurons (30 of 32) tested. The firing increased gradually, with a final control level of 130% (121-160%). In contrast, the GABAB receptor antagonist, phaclofen (20 microM and 100 microM), had no effect in most neurons (19 of 23) tested. Further, the excitatory and inhibitory action could be detected on the same neuron when bicuculline and kynurenate were both evaluated (n = 10). 6. These results indicate that the spontaneous discharge of MVN neurons is due to an endogenous pacemaker under the tonic influence of both inhibitory and excitatory transmitter actions. The bicuculline-sensitive GABAA receptors and the kynurenate-sensitive glutamate receptors both mediate the tonic modulation.

Amino Acids↗

Two groups of secondary vestibular neurons mediating horizontal canal signals, probably to the ipsilateral medial rectus muscle, under inhibitory influences from the cerebellar flocculus in rabbits.

Vestibular nuclear neurons that mediate horizontal canal signals to the ipsilateral medial rectus motoneurons were explored in anesthetized and decerebrate rabbits. These neurons were identified by four criteria: (1) they were activated monosynaptically by ipsilateral vestibular nerve stimulation and (2) antidromically from the oculomotor nucleus region, while they were inhibited by (3) direct floccular stimulation and (4) ipsilateral retinal stimulation that activated floccular Purkinje cells via a climbing fiber afferent pathway. Neurons fulfilling these criteria were found in two anatomically different regions, i.e. the rostrolateral part of the medial vestibular nucleus and in the ventral part of the lateral vestibular nucleus. In decerebrate rabbits, neurons in both loci responded to horizontal rotation of the whole body with the type I pattern (excited by ipsilateral rotation). These results suggest that horizontal canal signals are conveyed to ipsilateral medial rectus motoneurons by two separate groups of vestibular nuclear neurons which may play different roles in the vestibulo-ocular reflex.

Animals↗

Intrinsic membrane properties and dynamics of medial vestibular neurons: a simulation.

The vestibulo-ocular and vestibulo-spinal network provides the ability to hold gaze fixed on an object during passive head movement. Within that network, most of the second-order neurons of the medial vestibular nucleus (MVNn) compute internal representations of head movement velocity in the horizontal plane. Our previous in vitro studies of the MVNn membrane properties indicated that they may play a major role in determining the dynamic properties of these neurons independently of their connectivity. The present study investigated that hypothesis at a theoretical level. Biophysical models of type A and B MVNn were developed. Two factors were found to be important in modeling tonic and phasic firing activity: the activation of the delayed potassium current and the rate of calcium flux. In addition, the model showed that the strength of the delayed potassium current may determine the different forms of action potentials observed experimentally. These two models (type A and B cells) were examined using depolarizing stimulation, random noise, step, ramp and sinusoidal inputs. For random noise, type A cells showed stable (regular) firing frequencies, while type B cells exhibited irregular activity. With step stimulation, the models exhibited tonic and phasic firing responses, respectively. Using ramp stimulations, frequency versus current curves showed a linear response for the type B neuron model. Finally, with sinusoidal stimulation of increasing frequencies, the type A model demonstrated a decrease in sensitivity, while the type B model exhibited an increase in sensitivity. These theoretical results support the hypothesis that MVNn intrinsic membrane properties specify various types of dynamic properties amongst these cells and therefore contribute to the wide range of dynamic responses which characterize the vestibulo-ocular and vestibulo-spinal network.

Action Potentials↗

Vestibular neuronal function of cats following unilateral vertebral artery occlusion.

Since vertigo is known to be caused by vertebrobasilar arterial occlusive disease (ex. vertebrobasilar insufficiency; VBI), an electrophysiological study was performed to examine the effects of a unilateral vertebral artery (VA) occlusion on the neuronal activities of the medial vestibular nucleus (MVN) and vestibular ganglion (VG) in alpha-chloralose-anesthetized cats. Single neuronal activity in the MVN and VG was recorded extracellularly with a glass-insulated silver wire microelectrode. When the unilateral VA was occluded for 5 min. the spontaneous firing rate in the MVN was altered as follows. The type A pattern exhibited a transient increase, followed by a decrease. The type B pattern showed a gradual decrease, and no further changes after the onset of occlusion. Type A and B patterns were observed respectively in MVN ipsi- and contra-lateral to the VA occlusion. In contrast, the VG neuronal firing rate was not affected by the occlusion. These results seem to support the clinical suggestion that the vertigo in VBI is produced by a difference in the function between the bilateral vestibular nuclei. rather than by the peripheral vestibular nerve.

Animals↗

Central compensation of vestibular deficits. III. Response characteristics of lateral vestibular neurons to roll tilt after contralateral labyrinth deafferentation.

The responses of lateral vestibular nucleus (LVN) neurons to stimulation of macular labyrinth receptors have been investigated in precollicular decerebrate cats after contralateral acute vestibular neurectomy (aVN). On the whole, 78 LVN neurons were tested during slow sinusoidal tilt of the animal at the standard parameters (0.026 Hz, 10 degrees peak displacement). The neurons were located in both the rostroventral (rvLVN) and the dorsocaudal parts (dcLVN) of Deiters' nucleus, which project mainly to the cervical and the lumbosacral cord, respectively. After contralateral aVN, the proportions of responsive units in rvLVN and dcLVN (100% and 75.4%, respectively) were similar to those obtained in control experiments with intact labyrinths. However, the mean discharge rate of the responsive units slightly decreased with respect to the value obtained in control experiments, the decrease being more prominent within the rvLVN. The average sensitivity (and to a lesser extent the gain) of responses of rvLVN neurons to the labyrinth input was almost twice that of the dcLVN units in preparations with the vestibular nerves intact; these regional differences disappeared after contralateral aVN, particularly due to a decrease in gain and sensitivity of responses in the rvLVN. The proportion of LVN neurons that were maximally excited by animal position increased from 74.0% in the control experiments to 82.8%. However, while in control experiments the proportion of units excited during side-down tilt was twice as high as that of the units excited by side-up tilt, the opposite occurred after contralateral aVN; this finding affected particularly the dcLVN. In addition the average phase lead of responses relative to the extreme animal displacements slightly decreased from +12.3 degrees in control experiments to +9.4 degrees. Among the LVN neurons recorded after contralateral aVN, 35 were antidromically activated by stimulating the spinal cord at T12 L1, while 43 units were not activated. The relation found in control experiments, i.e., that the faster the conduction velocity of vestibulospinal axon the lower was the unit discharge at rest, was lost after contralateral aVN, due to a decrease in resting discharge rate of the slow neurons. This finding, coupled with the observation that slow and fast units did not show any difference in their response gain to tilt, explains why the positive correlation between axonal conduction velocity and response sensitivity occurring in control experiments was lost after contralateral aVN.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

Central compensation of vestibular deficits. IV. Responses of lateral vestibular neurons to neck rotation after labyrinth deafferentation.

The response characteristics of neurons located in the lateral vestibular nucleus (LVN) to neck rotation at 0.026 Hz, 10 degrees peak displacement, have been investigated in precollicular decerebrate cats submitted to ipsilateral acute (aVN) or chronic vestibular neurectomy (cVN). On the whole, 105 units were tested after aVN (i.e., during the first postoperative hours) and 132 units after cVN (i.e., after full compensation of the postural and locomotor deficits). The neurons were histologically located either in the rostroventral (rvLVN) or the dorsocaudal part (dcLVN) of Deiters' nucleus, which are known to project mainly to the cervical and the lumbosacral cord, respectively. Moreover, 55 units in the former group and 66 units in the latter group were identified as vestibulospinal neurons projecting to lumbosacral segments of the spinal cord. The responses of these 237 LVN neurons to the neck input were then compared with those of 120 LVN neurons recorded previously in decerebrate cats with intact labyrinths. Whereas 58.3% of the LVN units recorded in control experiments were responsive to neck rotation, 69.5% of the units were affected by this stimulation at the acute stage of the neurectomy and 74.2% at the chronic stage. This increase in responsive units after aVN and cVN with respect to the controls was found exclusively in the dcLVN. The mean discharge rate of the responsive LVN neurons decreased from 40.7 +/- 48.9 (SD) imp/s in control experiments to 22.1 +/- 15.8 (SD) imp/s after a VN. Similar value was also obtained after cVN [25.0 +/- 17.2 (SD) imp/s], suggesting that compensation of the postural deficits elicited by the vestibular neurectomy results from a redistribution of the excitatory drive within different populations of LVN neurons. Indeed, the relation found in control experiments, i.e., that the faster the conduction velocity of vestibulospinal axons the lower was the unit discharge at rest, was lost after aVN, due to a decrease in resting discharge of the slow units. The mean discharge rate of the slow units, however, recovered after cVN, so that the negative correlation between resting discharge rate and axonal conduction velocity was reestablished. The average gain and sensitivity of the first harmonic response of the LVN neurons to neck rotation recorded after aVN and cVN were comparable to those obtained in preparations with the vestibular nerves intact.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

Modulation by acute stress of chloride permeation across microdissected vestibular neurons membranes: different results in two rabbit strains and CRF involvement.

Free hand isolation of adult rabbit vestibular Deiters' neurons and dissection of their single membranes allows the study of their ionic permeability characteristics in a microchambers device. In the case of hare-like rabbits, the dissection of such membranes presents evidence of a high basal permeation of labelled chloride, possibly related to mechanical disturbance of the plasma membrane-related cytoskeleton and activation of chloride channels. This did not apply to the laboratory strain of white New Zealand rabbits. However, membranes from hare-like rabbits which were stressed by being rotated on a platform before the experiment, behaved like those from the New Zealand strain. Vice versa, habituation to handling day after day of New Zealand rabbits resulted in a chloride permeation equal to that of unstressed hare-like rabbits. We propose that the stressful conditions result in the release of neurochemical messages to the vestibular Deiters' cells which influence their electrophysiological behavior. The corticotropin releasing factor (CRF), a stress-related peptide present in the climbing fibers, actually blocks the basal chloride permeation across the Deiters' membranes and this effect is partially reversed by its receptor antagonist, alpha-helical CRF [9-41].

Acute Disease↗

Developmental study of rat vestibular neuronal circuits during a spaceflight of 17 days.

The aim of this study was to investigate the potential plasticity of the vestibular system, in structural and biochemical terms, at the level of the gravity receptors (the sensory hair cells), the primary neurons relaying the sensory signals (the vestibular ganglion neurons) and their projections into the vestibular nuclei. We studied the biochemical differentiation of the sensory cells and of the vestibular ganglion by investigating which calcium-binding proteins were present. We studied the development of peripheral synaptic connections of the efferent system by investigating the distribution of CGRP (calcitonin-gene related-peptide) and we also studied the cerebellar synaptic connections in the vestibular nuclei, as identified by the presence of calbindin. Putative changes were studied after a 17-day episode of microgravity (Neurolab STS-90), in developing rats between postnatal days 8 and 25. The extent to which these changes could be caused by alterations in gravity was determined by examining sensory and nervous structures not involved in gravity detection, the cochlea and the cochlear nuclei.

Acoustic Maculae↗

Rapid compensatory changes in GABA receptor efficacy in rat vestibular neurones after unilateral labyrinthectomy.

1. The inhibitory effects of the GABAA agonist muscimol and the GABAB agonist baclofen on tonically active medial vestibular nucleus (MVN) neurones were recorded in slices of the rat dorsal brainstem in vitro, to determine whether any changes occurred in the functional efficacy of GABAergic inhibition in these cells during the initial rapid stage of 'vestibular compensation', the behavioural recovery that takes place after unilateral labyrinthectomy (UL). These experiments were carried out in preparations where the midline was cut, severing all commissural connections between the two vestibular nuclei. 2. Slices of the MVN were prepared from normal animals and animals that had been unilaterally labyrinthectomised 4 h earlier. The mean in vitro discharge rate of MVN neurones in the rostral region of the ipsi-lesional nucleus after UL was significantly higher than that in control slices, confirming our earlier reports of an increase in intrinsic excitability of these cells in the early stage of vestibular compensation. The in vitro discharge rates of caudal ipsi-lesional MVN cells, and rostral and caudal contra-lesional MVN cells, were not different from controls. 3. Muscimol and baclofen caused reversible, dose-related inhibition of the tonic discharge rate of MVN cells in control slices. In slices prepared from UL animals, MVN cells in the rostral region of the ipsi-lesional nucleus showed a marked downregulation of their response to both muscimol and baclofen, seen as a rightward shift and a decrease in slope of the dose-response relationships for the two agonists. In the contra-lesional nucleus, there was a small but significant upregulation of the responsiveness of both rostral and caudal MVN cells to baclofen, and a marked upregulation of the responsiveness of caudal MVN cells to muscimol. 4. In slices from animals that had undergone bilateral labyrinthectomy 4 h earlier, the downregulation of the functional efficacy of GABA receptors in the rostral MVN cells did not occur. The changes in GABA receptor efficacy after UL are therefore not due to the vestibular de-afferentation itself, but are instead due to the imbalance in excitability of the vestibular nuclei of the lesioned and intact sides, and the enhanced commissural inhibition of the ipsi-lesional MVN cells that follows UL. 5. The downregulation of GABA receptor efficacy in the ipsi-lesional MVN neurones is functionally compensatory, in that their response to commissural and cerebellar inhibitory drive will be significantly reduced after UL. Their intrinsic membrane conductances, and their remaining excitatory synaptic inputs, will consequently be more effective in causing depolarisation and the restoration of resting activity. Simultaneously the upregulation of GABAergic efficacy in the contra-lesional MVN will tend to reduce the hyperactivity on the contralateral side. These adaptive changes therefore represent a plausible cellular mechanism for the recovery of resting discharge in the ipsi-lesional MVN neurones, and the 're-balancing' of the excitability of the vestibular neurones of the lesioned and intact sides, as occurs after UL in vivo. 6. We propose that the adaptive regulation of the functional efficacy of GABA receptors in the MVN neurones may be an important cellular mechanism for the 'homeostasis of bilateral excitability' of the vestibular nuclei of the two sides.

Action Potentials↗