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PubMed1986

Involvement of the inferior olivary neurons in vestibular compensation.

Vestibular decompensation induced by spinal cord transection in left labyrinthectomized guinea pigs provoked asymmetrical excitability of the inferior olivary nuclei. In the right nucleus, spinal deafferentation induced a significantly increased response to electrical stimulation of the contralateral radial nerve and decreased response to ipsilateral radial nerve stimulation. In the left nucleus, opposite results were obtained. Increased responses were recorded in the I.O. neurons during electrical stimulation of the radial nerve ipsilateral to a previous hemilabyrinthectomy, and reduced responses during the electrical stimulation of the radial nerve of the opposite side. Since the inferior olive impinges on the vestibular nuclei both directly and indirectly through the cerebellar loop, it is possible that the inferior olive is involved in the spinal compensation of the vestibular deficits resulting from the hemilabyrinthectomy.

Animals↗
PubMed2000

Unraveling of important neurobiological mechanisms by the use of pure, fully differentiated neurons obtained from adult animals.

An important, and often overlooked, problem in the neurochemical approach to neurobiological problems is that analysis of tissue involves almost always a heterogeneous population of cells (neurons, glia and other types of tissue cells). The use of cell cultures has obvious limitations such as that they derive from embryonic or immediately postnatal animals; in addition, the cell culture conditions most certainly are quite different from the real tissue environment for the nerve cells. We underline here an alternative strategy, which is not new, but which, in our view, has already given formidable contributions to neurobiological studies and still is giving results of great importance. This is the technique proposed and used since the late fifties and early sixties by the senior author (H. Hydén). The method involves the isolation of the big vestibular neurons from the adult rabbit vestibular nucleus. The neurons, fully differentiated and performing a precisely defined function, are obtained rapidly and completely free from surrounding glial cells. The separate microbiochemical study of these cells and their surrounding glia has yielded already in 1962, the information that modifications in gene expression are associated with plastic modifications of the function of the relevant neurons, which take place in the behavioral event of learning. Another important concept was formulated in the same time period following determination of the activities of energy metabolism related enzymes separately in vestibular neurons and their glia under vestibular stimulation. This is the concept that, under increased functional activity glia increases its anaerobic metabolism and passes then on the resulting metabolites to the neurons for aerobic metabolism. Both these concepts (RNA and memory; metabolic cooperation between glia and neurons) are nowadays widely accepted. In addition, this approach with pure big nerve cells has allowed in recent years the discovery of a novel mechanism for chloride extrusion in these cells. This mechanism utilizes structures similar to GABA activated chloride channels in cyclic modifications resulting in the final extrusion of chloride ions. The energy for the process is provided by a protein phosphorylation step. Future approaches are warranted such as the possibility of recognizing by RT-PCR specific neuronal mRNAs and their modification in expression in relation to function and plastic modifications (learning). Another possible interesting application appears to be the recognition of the mRNAs for GABA(A) receptor subunits expressed here in these neurons in relation to the physiological and pharmacological characteristics of these native neuronal GABA(A) receptors.

Animals↗
PubMed1994

Effect of caloric stimulation on primary vestibular fibers originating from otolith organs in the guinea pig.

The influence of caloric stimulation on the primary vestibular fibers originating from the otolith organ was investigated in the guinea pig. Firing rates were recorded from single vestibular neurons in the superior vestibular (Scarpa's) ganglion which were identified physiologically as originating from the otolith organs, mainly from the utricles. Eighty-six percent of the neurons responded to caloric stimulation. Neurons with a high coefficient of variation of firing regularity reacted more sensitively to tilting and also had a tendency to react more sensitively to caloric stimulation. There was a tendency for neurons with increased firing rates in response to ipsilateral tilting to have increased firing rates to warm stimulation, while neurons whose rates increased to contralateral tilting had increased firing rates to cold stimulation. These results indicate that the otolith organs have the same unidirectional tendency to caloric simulation with results comparable to optimal tilting directions.

Action Potentials↗
PubMed1990

Vestibulo-ocular projections in the 11-day chicken embryo: pathway specificity.

The organization of vestibulo-ocular projections and their spatial relationship to vestibulo-spinal projections were ascertained in the 11-day chicken embryo through retrograde tracing experiments. An in vitro preparation of the brainstem facilitated precisely localized application of tracers. Unilateral labelling of the ascending medial longitudinal fascicle (MLF), just caudal to the trochlear nucleus, labelled coherent groups of vestibular neurons that had an asymmetrical distribution on the two sides of the brainstem. Axons originating from either side followed one of four trajectories, and the groups of neurons could therefore be identified on the basis of their position and their projection pathway. Labelling each side of the MLF with a different tracer showed that although neurons projecting in the ipsi- and contralateral MLF were intermingled in some areas, individual neurons projected on one side only. Labelling the ascending MLF and the high cervical spinal cord with different tracers showed that vestibulo-ocular neurons had a wider rostro-caudal distribution than vestibulospinal neurons. Some vestibulospinal and vestibulo-ocular groups were spatially segregated, others were intermingled. Very few (in most preparations no) neurons were found to project to both targets. Together with our previous study on vestibulospinal projections in the 11-day chicken embryo (Glover and Pétursdóttir, J. Comp. Neurol. 270:25-38, '88) the results show that vestibular neurons in different regions project in characteristic subsets of the available pathways.

Afferent Pathways↗
PubMed1992

Brain-derived neurotrophic factor and neurotrophin 3 mRNAs in the peripheral target fields of developing inner ear ganglia.

In situ hybridization was used to study the site and timing of the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 5 (NT-5) mRNAs in the developing inner ear of the rat. In the sensory epithelia, the levels of NGF and NT-5 mRNAs were below the detection limit. NT-3 and BDNF mRNAs were expressed in the otic vesicle in overlapping but also in distinct regions. Later in development, NT-3 transcripts were localized to the differentiating sensory and supporting cells of the auditory organ and vestibular maculae. In these sensory epithelia, the intensity of NT-3 mRNA expression decreased in parallel with maturation. The expression of BDNF mRNA was restricted to the sensory cells of both the auditory and vestibular organs, including ampullary cristae. In bioassays, BDNF and NT-3, but not NGF, at physiological concentrations induced neurite outgrowth from the statoacoustic ganglion explants. These results demonstrate that NT-3 and BDNF, rather than NGF and NT-5, are the primary neurotrophins present in the target fields of the cochlear and vestibular neurons. Expression of NT-3 and BDNF mRNAs in the otic vesicle before and during the ingrowth of neurites from the statoacoustic ganglion suggests that NT-3 or BDNF or both may serve as chemoattractants for the early nerve fibers. The results also suggest that these neurotrophins have a role in later development of the cochlear and vestibular neurons.

Animals↗
PubMed1994

The organization of vestibulo-ocular and vestibulospinal projections in the chicken embryo.

The functional neuroanatomy of vestibulo-ocular and vestibulospinal projections has been studied in the chicken embryo as a step towards elucidating the developmental mechanisms that determine the connectivity patterns of the vestibular system. Retrograde and anterograde axonal tracing, neurotransmitter immunohistochemistry, and retrograde transport of radiolabelled neurotransmitters or neurotransmitter analogs demonstrate that vestibular neurons are clustered into functionally specific populations. Each of these has a characteristic positional domain, projection pathway, and site of termination. At early embryonic stages, the positional domains of the various populations are systematically correlated with segmental and longitudinal territories of differential gene expression in the hindbrain. The intimate link between position and phenotype at these stages suggests that the functional identity of vestibular neurons is determined, at least in part, by mechanisms associated with early pattern formation of the neural tube.

Animals↗
PubMed1988

A matrix analysis for a conjugate vestibulo-ocular reflex.

The technique of matrix analysis is used to compare the connectivity between vestibular neurons and oculomotor neurons of the two eyes that would generate a conjugate vestibulo-ocular reflex (VOR). The technique shows that the connectivity is normally anatomically symmetric. The technique is also used to determine the types and loci of adaptation within the VOR that will maintain conjugacy. Adaptation is divided into 1) that evoked by changes in visual feedback, which requires VOR or system-specific changes and 2) that produced by changes in the canals or muscles, which requires deficit-specific adaptation. In the former case, the adaptation could best be achieved by an additive alteration of the vestibular-motoneuron projections. In the latter case, the appropriate adaptations would be serial, multiplicative changes, applied at the level of the vestibular neurons when the canals are at fault or at the level of the motoneurons of the eye whose muscles are impaired. The analysis thus suggests multiple loci of plasticity within the VOR, specialized for adapting to different deficits.

Adaptation, Physiological↗
PubMedDate not supplied

Labyrinthine and somatosensory convergence upon vestibulospinal neurons.

In awake cats cells forming the lateral (LVST) and medial (MVST) vestibulospinal tracts were identified by employing antidromic stimulation of the spinal cord. Neuronal responses to bilateral vestibular, forelimb, hindlimb, and neck electrical nerve stimulation were analysed. Extracellular recording in the vestibular nuclei was performed via a glass micropipette saturated with Fast Green, to aid in later histological tract identification. The number of cells projecting to cervical and lumbar regions in the dorsal and ventral division of Deiters' nucleus did not differ significantly. An unexpectedly large number of MVST units was found in the descending nucleus. Some MVST units projected to the lumbar cord but in both the medial and descending nuclei, projections to the cervical cord were in majority. Almost all spinal projecting vestibular neurons received labyrinthine input and more than half received somatosensory input. The units could be separated into several populations on basis of excitatory and inhibitory labyrinthine response latencies indicating multiple pathways. As regards labyrinthine-somatosensory integration the two tracts were found to be quite similar. The extent and complexity of labyrinthine-somatosensory convergence indicate the importance of feed-back mechanisms upon postural controls also at the level of the vestibular nuclei.

Action Potentials↗
PubMed1978

Response characteristics of semicircular canal and otolith systems in cat. II. Responses of trochlear motoneurons.

1. The electrical activity of single trochlear motoneurons (TMns) and axons of second order vestibular neurons presumably terminating on these motoneurons were studied during natural stimulation of semicircular canals and otolith organs in cats anesthetized with Ketamine. 2. Null point analysis showed that TMns received an excitatory canal input from the contralateral posterior canal, and labyrinthine lesion experiments suggested that the functionally synergistic, ipsilateral anterior canal provides an inhibitory input. A small number of motoneurons showed orthogonal canal convergence. 3. In addition to the canal projections most TMns received an otolithic input. Firing rate was proportional to lateral head tilt and was of the beta type. Most units also responded to pitch with an increase and decrease in firing rate on nose-up and nose-down positioning, respectively. Lesion experiments indicated that the otolith responses are the results of reciprocal innervation of TMns by contralateral (excitatory) and ipsilateral (inhibitory) otolith projections. 4. During sinusoidal rotation in yaw (canal only stimulation) the mean phase lag re acceleration of the response of TMns increased from 60 degrees at 0.025 Hz to 126 degrees at 1.0 Hz. In roll (canal plus otolith stimulation) the phase lag of TMn responses measured 180 degrees and 130 degrees at 0.025 and 1.0 Hz, respectively. Phase-lags measured in Vi and Vc axons were less by ca. 15 degrees. 5. The otolith contribution to TMn responses in roll was calculated by vectorial subtraction of the yaw from the roll responses: A phase lag of 10 (0.025 Hz) to 90 degrees (0.5 Hz) re. displacement was noted and gain was constant over the same range. Similar lag dynamics were revealed in TMns when studied during ramp displacement of the head. 6. The possible functional role of central canal-otolith convergence and the differences between the response of primary vestibular afferents and secondary vestibular neurons and TMns will be discussed.

Animals↗
PubMed1983

Flocculectomy and unit activity in the vestibular nuclei during visual-vestibular interactions.

Activity of neurons in the vestibular nuclei of alert monkeys was recorded extracellularly after total unilateral and bilateral flocculectomy and partial paraflocculectomy. Type 1 horizontal cells that were encountered after flocculectomy responded to visual and vestibular stimuli and to conflict stimulation, i.e., to rotation in a subject-stationary visual surround, as do vestibular neurons in the normal animal. The major difference between neurons in the normal and lesioned animals was that more time was needed to reach steady state firing levels during optokinetic stimulation at a constant velocity after operation. As shown previously (Waespe et al. 1983) the longer time course is related to increased initial retinal slip velocities that occur after flocculectomy as a result of an inability to change eye velocity rapidly in response to visual stimulation. It does not signify a change in the dynamics of neurons in the vestibular nuclei that mediate the vestibulo-ocular reflex (VOR). The similarity in modulation of horizontal Type 1 vestibular neurons in normal and flocculectomized monkeys makes it unlikely that floccular Purkinje cells suppress the horizontal VOR in the monkey during conflicting visual and vestibular stimuli by inhibiting or disfacilitating secondary or tertiary vestibular neurons. This is consistent with earlier findings that indicate that visual-oculomotor pathways responsible for ocular pursuit or for rapid changes in OKN do not go through the vestibular nuclei. Rather the point of interaction of the flocculus output with the VOR appears to be external to the vestibular nuclei. There was a close correspondence between the slow phase velocity of nystagmus and unit activity in the vestibular nuclei under a wide variety of test conditions after flocculectomy. This is consistent with the postulate that frequencies of vestibular nuclei neurons represent a summation of activity in direct vestibulo-oculomotor pathways and indirect pathways that include the velocity storage mechanism. These are the major remaining sources of activity that generate slow phases of nystagmus after the direct visual-oculomotor pathways have been partially interrupted by flocculectomy (Waespe et al. 1983). Horizontal Type 1 neurons which responded to vestibular and optokinetic stimulation with increases in frequency above 1 spike/s/degree/s were rarely encountered after flocculectomy. These cells were present on the normal side in a monkey after unilateral flocculectomy. We infer that vestibular nuclei neurons that project mossy fibers to the flocculus are inactivated or disappear as a result of surgical ablation of their axons. This could also contribute to the reduced gain of vestibular nystagmus, OKAN and off-vertical nystagmus that was observed in some of the animals after lesion.

Animals↗
PubMed1981

[Scarpa's ganglion with increasing age, in Menière's disease and otosclerosis (author's transl)].

A quantitative study of primary vestibular neurons was performed in temporal bones of individuals at different ages. The mean numbers of counts decreased beginning in the age group between 50 and 60 years. Neuronal populations from cases with Menière disease and otosclerosis were compared to the respective "normal" values. Endolymphatic hydrops could be excluded as the cause of degeneration of Scarpa's ganglion in Menière' disease. In cases of otosclerosis reduced neuronal counts were found if lesions were large enough to include the cribrose areas.

Adolescent↗
PubMedDate not supplied

Neuronal responses in vestibular nuclei to dorsal raphe electrical activation.

The effects of dorsal raphe (DR) electrical stimulation on the neuronal activity of vestibular nuclei were studied in anaesthetized rats. The aim was to establish whether the central systems classically involved in nociceptive functions are able to influence vestibular secondary neurons. DR activation induced modifications of the firing in 70% of the tested neurons, the percentage being similar in the lateral (LVN), superior (SVN), and spinal (SpVN) vestibular nuclei. Three different types of responses were recorded: long-lasting modifications (generally enhancements) of the mean firing rate (43%), short-latency response patterns (14%), both (43%). Short-latency response patterns were more numerous in LVN than in SVN. Iontophoretic applications of 5-HT antagonists Methysergide and Ketanserin blocked long-lasting effects but were scarcely effective on the short-latency response patterns evoked by DR stimulation. It is concluded that DR exerts a double control on secondary vestibular neurons: a generalised excitatory influence by serotoninergic fibers and a specific action mostly targeted on LVN, by nonserotoninergic pathways.

Animals↗
PubMed1997

Physiological and anatomical study of click-sensitive primary vestibular afferents in the guinea pig.

We studied the sensitivity of primary vestibular afferents in anaesthetised guinea pigs to clicks. These vestibular neurons were also tested by their response to pitch and roll tilts and yaw-axis angular acceleration. The click intensity was referred to the threshold for evoking the auditory brainstem responses. Recording sites in the vestibular nerve were confirmed histologically using iontophoretic injection of FCF green dye. To confirm the site of labyrinthine origin of the click-sensitive neurons, we used retrograde tracing with biocytin. In all, 647 out of 2354 neurons in the vestibular nerves of 51 guinea pigs were activated by clicks. Most were irregularly discharging primary neurons, but some were regularly discharging. We studied responses to vestibular stimuli in 188 click-sensitive neurons. Of these, 86% responded to pitch and/or roll tilt, but none responded to yaw angular acceleration. Conversely we also recorded vestibular neurons which did not respond to clicks. None of 300 neurons sensitive to yaw angular acceleration were responsive to 80-90 dB SL clicks (0 dB SL = threshold for auditory brainstem response to clicks). The latencies of click-evoked action potentials of neurons in the vestibular nerve were very short (mean +/- SD = 0.82 +/- 0.22 ms). Changing click polarity caused a heterogeneous pattern of latency change. Thresholds for evoking spikes in primary vestibular neurons were high (62.0 +/- 12.2 dB SL, range 30-90 dB, n = 371). Retrograde tracing of the origin of the click-sensitive afferents using extracellular biocytin showed that most neurons originated in the medial (striola area) of the saccular macula.

Acoustic Stimulation↗