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Responses of reticulospinal neurons in intact lamprey to vestibular and visual inputs.

A lamprey maintains the dorsal-side-up orientation due to the activity of postural control system driven by vestibular input. Visual input can affect the body orientation: illumination of one eye evokes ipsilateral roll tilt. An important element of the postural network is the reticulospinal (RS) neurons transmitting commands from the brain stem to the spinal cord. Here we describe responses to vestibular and visual stimuli in RS neurons of the intact lamprey. We recorded activity from the axons of larger RS neurons with six extracellular electrodes chronically implanted on the surface of the spinal cord. From these multielectrode recordings of mass activity, discharges in individual axons were extracted by means of a spike-sorting program, and the axon position in the spinal cord and its conduction velocity were determined. Vestibular stimulation was performed by rotating the animal around its longitudinal axis in steps of 45 degrees through 360 degrees. Nonpatterned visual stimulation was performed by unilateral eye illumination. All RS neurons were classified into two groups depending on their pattern of response to vestibular and visual stimuli; the groups also differed in the axon position in the spinal cord and its conduction velocity. Each group consisted of two symmetrical, left and right, subgroups. In group 1 neurons, rotation of the animal evoked both dynamic and static responses; these responses were much larger when rotation was directed toward the contralateral labyrinth, and the dynamic responses to stepwise rotation occurred at any initial orientation of the animal, but they were more pronounced within the angular zone of 0-135 degrees. The zone of static responses approximately coincided with the zone of pronounced dynamic responses. The group 1 neurons received excitatory input from the ipsilateral eye and inhibitory input from the contralateral eye. When vestibular stimulation was combined with illumination of the ipsilateral eye, both dynamic and static vestibular responses were augmented. Contralateral eye illumination caused a decrease of both types of responses. Group 2 neurons responded dynamically to rotation in both directions throughout 360 degrees. They received excitatory inputs from both eyes. Axons of the group 2 neurons had higher conduction velocity and were located more medially in the spinal cord as compared with the group 1 neurons. We suggest that the reticulospinal neurons of group 1 constitute an essential part of the postural network in the lamprey. They transmit orientation-dependent command signals to the spinal cord causing postural corrections. The role of these neurons is discussed in relation to the model of the roll control system formulated in our previous studies.

Action Potentials↗

Spontaneous discharge and response characteristics of central otolith neurons of rats during postnatal development.

To study the developmental profile of otolith-related vestibular nuclear neurons, their spontaneous activities and response dynamics were examined in decerebrate rats aged seven, 14, 21 and 84 (adult) days. Extracellular recordings were performed in the lateral and descending vestibular nucleus of animals held at the stationary position in the earth-horizontal or subjected to constant velocity off-vertical axis rotation, which selectively stimulates the otolith receptors. All neurons displayed sinusoidal position-dependent modulation in discharge rate, indicating their capability in coding spatial information during low-frequency head movement. Some neurons showed a full-cycle response to off-vertical axis rotation (non-clipped), while other neurons were silenced in discharge during parts of each rotary cycle (clipped). In seven-day-old rats, three-quarters of the responsive neurons sampled were clipped and the proportion progressively decreased to less than one-quarter in adult rats. In each age group, the clipped neurons discharged in approximately 60% of the stimulus cycle. Response gains of the neurons increased with age, reaching a plateau from 21 days of age for clipped neurons and 14 days for non-clipped neurons. The clipped neurons demonstrated higher response gains than the non-clipped neurons at or beyond 21 days of age. Spontaneous activities of the neurons at the stationary and earth-horizontal positions were analysed in relation to their response gains; a positive correlation was observed from 14 days of age onwards. Both types of neurons showed progressive increase in spontaneous activity as the rats matured, though the clipped neurons exhibited significantly lower resting rates than the non-clipped neurons at each of the age groups studied. Some neurons that responded to off-vertical axis rotation were not spontaneously active at the stationary position, but the proportion of these decreased significantly with age. The coefficient of variation of each age group showed a bimodal distribution, thereby allowing spontaneously active neurons to be assigned as regular or irregular. Though the vast majority of both the clipped and non-clipped neurons showed irregular discharge patterns at seven days of age, the overall population became more regular as the rats matured. Irregular neurons of young rats exhibited phase-stable and phase-shift responses, while those of older rats showed only the phase-stable response. This distinction was not observed amongst regular neurons over the ages studied. Our results reveal features of central otolith neurons that can be taken as signs of maturation during the first three postnatal weeks. These neuronal features provide the framework for the analysis of behaviours mediated by the otolith system during postnatal maturation.

Action Potentials↗

Importance of the visual and vestibular cortex for self-motion perception in man (circularvection).

Circularvection (CV), the optokinetically induced perception of self-motion, is based neurophysiologically upon visual-vestibular convergence. It is yet not known which visual pathways--subcortical accessory optic tract and/or cortical striate projection--convey optokinetic information to the central vestibular system in order to make possible the convergence that has been found: the vestibular nuclei, the thalamus and the vestibular cortex. The functional significance of the visual cortex was demonstrated in 12 patients with homonymous hemianopia who neither perceived CV nor exhibited a postural destabilization when exposed to optokinetic pattern motion (yaw or roll) restricted to the scotoma. The functional significance of the vestibular cortex as well as ipsilateral visual-vestibular interaction was demonstrated in 4 (out of 20) patients with tumour lesions involving the vestibular cortex areas. They either failed to perceive CV or showed a significant increase of CV-latencies when monocular optokinetic stimulation was restricted to the ipsilateral visual cortex. Arguments for and against the following hypothesis are discussed: circularvection is induced by visual motion stimulation of the primary visual cortex which then activates vestibular nuclei neurons by descending pathways and which also informs the vestibular cortex that self-motion with a perceptual direction is involved. Determination of the velocity of CV is mediated by direct visual-vestibular cortex interaction, which most probably is also involved in the perceptual interpretation of motion perception: Self-motion versus object-motion.

Adult↗

[Vestibulocochlear anastomosis in the brain stem of the guinea pig. Preliminary report].

A conspicuous fibre bundle running through the vestibular nuclear complex into the cochlear nucleus could be detected after tracing the superior vestibular nerve branch and the macula sacculi of the guinea pig with HRP (horseradish peroxidase). Considering certain electrophysiological findings, it is quite reasonable to believe that these fibres are indeed primary vestibular afferent fibres in synaptic contact with secondary cochlear neurons.

Afferent Pathways↗

Effects of acute hypotension on neuronal activity in the medial vestibular nuclei of rats.

The role of peripheral vestibular receptors in acute hypotension was investigated in anesthetized rats. In animals with intact labyrinths, acute hypotension induced by either i.v. infusion of sodium nitroprusside or hemorrhage produced excitation of electrical activity in two-thirds of type I neurons and inhibition in two-thirds of type II neurons recorded in the medial vestibular nuclei. In unilaterally labyrinthectomized animals, two-thirds of type I neurons ipsilateral to the lesion showed an inhibitory response, and two-thirds of contralateral type I neurons showed an excitatory response after the induction of acute hypotension. The response patterns of type II neurons were opposite to those of type I neurons. These results suggest that blood flow changes are detected by peripheral vestibular receptors, and that this might suggest a mechanism for control of blood pressure.

Action Potentials↗

[Excitatory effects of glucocorticoids on neuronal activity in the medial vestibular nucleus--mediation by glucocorticoid receptor on the membrane].

Although glucocorticoids are sometimes used for the treatment of vertigo in certain disorders such as Meniere's disease, the mechanism underlying anti-vertigo effect remains unknown. The present study was performed to examine the effects of a glucocorticoid, dexamethasone, on neuronal activity in the medial vestibular nucleus (MVN) to determine whether or not the drug acts directly on the MVN neuron using alpha-chloralose-anesthetized cats which were fixed in a stereotaxic instrument placed on a turn-table. Single neuronal activities in the MVN were extracellularly recorded with a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette. Each pipette was filled with dexamethasone phosphate (0.1 M), monosodium glutamate (1 M), glutamic acid diethylester (GDEE) (0.05 M: a non-selective glutamate receptor antagonist), CoCl2, (0.1 M: a non-specific calcium channel blocker), RU38486 (0.01 M: glucocorticoid receptor antagonist) or potassium canrenoate (0.1 M: a mineralo-cortical receptor antagonist). These chemicals were microiontophoretically applied to the immediate vicinity of the target neuron being recorded. The effects of the drugs were examined on type I neurons which were identified according to responses to rotation: the neuron showed an increase and a decrease in firing with ipsilateral and contralateral rotation to the recording site, respectively. Microiontophoretically applied dexamethasone (50-200 nA) dose-dependently increased spontaneous firing of MVN neurons. However iontophoretic application of GDEE did not affect the dexamethasone-induced increase in firing of the MVN neurons but inhibited glutamate- and rotation-induced firing. Microiontophoretically applied Co2+ did not affect dexamethasone-, glutamate- and rotation-induced firing. However, dexamethasone-induced firing was dose-dependently suppressed by iontophoretic RU38486, but not by canrenoate. Then a microdialysis study using alpha-chloralose-anesthetized cats was performed to determine whether or not dexamethasone affects the release of glutamate from vestibular nerve terminals. The microdialysis probe (CMA/10, 2 mm) was inserted into the MVN and perfused with Ringer solution at 2 ml/min. Samples were collected at 10-min intervals. Endogenous glutamate was measured using the HPLC-ECD method. When repetitive stimuli (200 microseconds duration, 0.5 mA and 5 Hz) were given to the vestibular nerve for 10 min, an increase in the release of glutamate was observed. Dexamethasone did not produce spontaneous or stimulation-induced release of glutamate. These results suggest that dexamethasone acts directly on the MVN neuron to excite neuronal activity through glucocorticoid receptors on neuron membranes, but the excitation is not due to the release of glutamate.

Animals↗

A mathematical model for the mechanism of rapid eye movements induced by an anticholinesterase in the decerebrate cat.

The oculomotor pattern which appears in intact preparations during desynchronized sleep is characterized by the irregular occurrence of isolated ocular movements and bursts of rapid eye movements (REM). This complex oculomotor pattern results from the activity of two premotor structures which influence the extraocular motoneurons during this phase of sleep: one is located in the pontine reticular formation, the other in the vestibular nuclei. In the decerebrate preparation the intravenous injection of an anticholinesterase leads to the appearance of a typical pattern of oculomotor activity, which differs from that occurring during physiological sleep in so far as it consists quite exclusively of bursts of REM which appear at very regular intervals. Lesion experiments as well as unit recordings have shown that these bursts of REM depend in particular upon rhythmic discharges of the vestibular nuclear neurons. The underlying anatomical structures responsible for these bursts of REM are therefore the vestibular nuclei, the oculomotor nuclei and the oculo-orbital system. This mechanism is under the influence of cholinergic reticular neurons which generate the oculomotor rhythm. We have postulated the existence of a self-excitatory cholinergic system, located in the pontine reticular formation, whose steady discharge impinges upon an oscillatory neuronal system located in the dorso-lateral pontine tegmentum, which transforms the tonic input into a sinusoidal final output. We have assumed also that the periodic increases in the discharge frequency of this oscillatory system trigger a fast phase generator acting on the different components of the REM system, and that the behavior of each component follows a first-order differential equation. The state of excitation of the components of the system is defined as proportional to frequency of nerve impulses. Assuming ipsilateral and crossed connections, a pattern of oculomotor activity is obtained that simulates the experimental oculomotor output fairly well. The repetition of the eye jerks is described by a Fourier series. The model proposed in this paper may be taken as a first approach in describing the generation mechanism of REM, and as a theoretical guide to new experimental researches and the development of other more realistic models.

Animals↗

Single neuron activity related to natural vestibular stimulation in the cat's visual cortex.

This study examines the possibility of a vestibular input to the visual cortex using chronically implanted cats subjected to horizontal sinusoidal rotation in the dark. In areas 17 and 18 the activity of respectively 14% and 11% of units was modified by vestibular stimulation. Both non-specific and specific influences were observed. Specific influences (42% in area 17 and 33% in area 18) were similar to the types of responses recorded in the vestibular nuclei, and were encountered more frequently within the cortex subserving the peripheral visual field. Our results could provide a neurophysiological basis for some psychophysiological observations concerning visuo-vestibular interactions.

Animals↗

Neuronal activity in the contralateral medial vestibular nucleus of the guinea pig following unilateral labyrinthectomy.

The recovery of normal ocular motor and postural behavior following unilateral labyrinthectomy is termed vestibular compensation and it has been attributed to the return of normal resting activity to neurons in the bilateral vestibular nuclei. Previous studies in the cat have reported that approximately normal resting activity returns to type I neurons in the medial vestibular nucleus (MVN) contralateral to the deafferentiation by 4-8 weeks post-operation (post-op.), while the gain of the response of these neurons to horizontal angular acceleration remains lower than normal. The present data demonstrate that, in the guinea pig, normal resting activity returns to the contralateral MVN type I neurons by only 52-60 h post-op., while the gain and phase of the response of these neurons to horizontal sinusoidal acceleration remains abnormal up to 8-12 months post-op. By contrast with previous studies, the present data show that type II neurons in the contralateral MVN exhibit some increase in their frequency of occurrence and gain toward normal values during vestibular compensation (at 52-60 h and 8-12 months post-op.). The rapid recovery of normal type I resting activity correlates with the disappearance of spontaneous nystagmus and postural asymmetries in the guinea pig by 52 h post-op.

Animals↗

Neuronal loss in human medial vestibular nucleus.

The data concerning the effects of age on the brainstem are inconsistent, and few works are devoted to the human vestibular nuclear complex. The medial vestibular nucleus (MVN) is the largest nucleus of the vestibular nuclear complex, and it seems to be related mainly to vestibular compensation and vestibulo-ocular reflexes. Eight human brainstems have been used in this work. The specimens were embedded in paraffin, sectioned, and stained by the formaldehyde-thionin technique. Neuron profiles were drawn with a camera lucida at x330. Abercrombie's method was used to estimate the total number of neurons. We used the test of Kolmogorov-Smirnov with the correction of Lilliefors to evaluate the fit of our data to a normal distribution, and a regression analysis was performed to determine if the variation of our data with age was statistically significant. The present study clearly shows that neuronal loss occurs with aging. The total number of neurons decreases with age, from 122,241 +/- 651 cells in a 35-year-old individual to 75,915 +/- 453 cells in an 89-year-old individual. Neuron loss was significant in the caudal and intermediate thirds of the nucleus, whereas the changes in the rostral third were not significant. The nuclear diameter of surviving neurons decreased significantly with age. There is a neuron loss in the MVN that seems to be age-related. It could help explain why elderly people find it hard to compensate for unilateral vestibular deficits. The preservation of neurons in the rostral third could be related to the fact that this area primarily innervates the oculolmotor nuclei; these latter neurons do not decrease in number in other species studied.

Adult↗

[Vestibulofugal projections to the lateral reticular nucleus of the cat medulla].

Certain amount of neurons in vestibular nuclei were labelled after horseradish peroxidase injection in the medullar lateral reticular nucleus of cat. Such projections were strictly homolateral and formed by small and medium-size neurons localized mainly in the Deiters nucleus; their number was, probably, much less in comparison with the number of vestibulo-spinal units. Functional role of vestibular projections to the lateral reticular nucleus in the motor activity control is discussed.

Animals↗

Responses of ventral respiratory group neurons of the cat to natural vestibular stimulation.

Stimulation of vestibular otolith afferents by fore-aft tilt (pitch) elicits changes in activity of nerves innervating respiratory muscles, including the diaphragm, abdominal muscles, and tongue musculature. To determine the role of ventral respiratory group (VRG) neurons in producing these vestibular-respiratory responses, the activity of VRG neurons was recorded during natural vestibular stimulation in multiple transverse planes. Only a small fraction of VRG neurons with inspiratory (I, 20 of 80 cells), expiratory (E, 11 of 59 cells), or phase spanning (4 of 16 cells) activity responded to tilts up to 15 degrees in amplitude delivered at frequencies from 0.02 to 2 Hz. In particular, responses were infrequent in VRG neurons with projections to the spinal cord (0 of 23 E cells and 2 of 15 degrees I cells), despite the fact that the tilts employed produced robust modulation of the activity of abdominal (expiratory) nerves. Furthermore, the characteristics of responses to tilt of the small fraction of VRG neurons with vestibular inputs did not match those of respiratory muscles. These data suggest that neurons in addition to those in the VRG must participate in generating vestibular-respiratory responses.

Abdominal Muscles↗

Neuronal degeneration of primary cochlear and vestibular innervations after local injection of sisomicin in the guinea pig.

This paper reports on a dynamic study of the morphological changes within the cochlear and vestibular ganglia of the guinea pig after local application of Sisomicin in the inner ear. The treatment leads to a rapid, complete and irreversible destruction of the sensory cells in the cochlear and vestibular neuroepithelia. A progressive degeneration of the type I and type II afferent neurons, presenting a decreasing gradient from the base towards the apex of the cochlea, is rapidly observed and becomes almost complete as early as 15 days after the peripheral injury. Five months after the treatment the spiral ganglion cells have almost completely disappeared. At this time the vestibular ganglion cell density appears normal but the neurons exhibit important signs of alteration. Such damage to the cochlear and vestibular afferent neurons may result from either retrograde neuronal degeneration and/or direct neurotoxic effect of the drug. Thus the combination of the two mechanisms could lead to neuronal losses in spiral and Scarpa's ganglia after the local aminoglycoside intoxication of the inner ear. The difference in the time course of degeneration for these two afferent ganglia could be due to their specific susceptibilities or to their different anatomical locations.

Animals↗

The hypothesis of the uniqueness of the oculomotor neural integrator: direct experimental evidence in the cat.

1. As far as horizontal eye movements are concerned, the well-known hypothesis, not yet experimentally proved, of the common neural integrator states that the eye-position signal is generated by a common network, regardless of the type of versional movement. The aim of this study was to evaluate the validity of this hypothesis by checking whether the sensitivity to eye position of the neurones of the nucleus prepositus hypoglossi (NPH) (the main component of the system integrating the different incoming velocity signals) would be the same regardless of the type of versional movement. 2. The discharge of sixty-five NPH neurones was recorded in the alert cat during spontaneous eye movements made in the light and in response to sinusoidal rotations of the head in complete darkness. 3. For each NPH neurone, the sensitivity to eye position was determined from measurements carried out during intersaccadic fixation. The discharge rate of the studied neurone was plotted against eye position. The slope of the resulting regression line gave the sensitivity (measured during intersaccadic fixation in the light) of the neurone to eye position, which was termed K(f). 4. A new method was developed to measure the sensitivity to eye position (K(v)) of neurones during vestibular slow phases. The difficulty came from the fact that, during slow phases, eye velocity and eye position changed simultaneously and that each of those two variables could influence neuronal activity. For each neurone, the instantaneous firing rate was measured each time the eye passed through a given position during any slow phase generated during any vestibulo-ocular reflex. At a given position, the discharge rate of the neurone under study was plotted against the eye velocity. From the resulting linear regression line, two interesting values were obtained: its slope, corresponding to the sensitivity of the neurone to eye velocity, R(v), (at that given eye position) and its 'y'-intercept, F(0), the interpolated firing rate when the eye velocity was zero. This procedure was repeated for different eye positions. The values of F(0) were then plotted against the eye positions. The slope of the resulting regression line gave the sensitivity (measured during vestibular stimulation) of the neurone to eye position, which was termed K(v). 5. The errors on the individual values of K(f) and K(v) were assessed in order to allow a statistical comparison at the single unit level. 6. We found that, for each of our sixty-five neurones, the sensitivity to eye position measured during intersaccadic fixation in the light was equal to the sensitivity to eye position measured during the vestibulo-ocular reflex (VOR) elicited in complete darkness. We conclude that our results favour the hypothesis of a unique horizontal oculomotor integrator for all versional movements.

Animals↗