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PubMed2004

Zonal organization of the vestibulo-cerebellum in the control of horizontal extraocular muscles using pseudorabies virus: I. Flocculus/ventral paraflocculus.

Much literature has studied the relationship between the organization of neurons in the flocculus/ventral paraflocculus and vestibulo-ocular reflex pathways. Although activation of a flocculus central zone produces ipsilateral horizontal eye movement, anatomical tracing evidence in rats suggests that there may not be a simple one-to-one correspondence between flocculus/ventral paraflocculus zones and control of single extraocular muscles or coplanar pairs of antagonistic extraocular muscles. This study used the retrograde transynaptic transport of pseudorabies virus to identify the topographical organization of Purkinje cells in the flocculus/ventral paraflocculus that control the lateral rectus (LR) and medial rectus (MR) muscles in rats. A survival time of 80 h and 84 h was necessary to observe consistent transynaptically labeled cells in the flocculus/ventral paraflocculus following injections of pseudorabies virus into the MR and LR, respectively. The organization of Purkinje cells in the dorsal flocculus and ventral paraflocculus abided by the traditional boundaries, whereas the labeling pattern in the ventral flocculus showed a more complex, interdigitated arrangement. In agreement with prior studies, transynaptically labeled neurons were also observed in specific vestibular nuclear regions within the medial and superior vestibular nuclei and dorsal Y group. The distribution of labeled neurons in ipsilateral and contralateral vestibular nuclei was associated with features of ipsilateral and contralateral retrograde labeling of Purkinje cells in flocculus/ventral paraflocculus. Importantly, this study provides the first evidence of vestibulo-cerebellar zones controlling individual extraocular muscles and also overlapping distribution of neurons in flocculo-vestibular zones that influence the LR and MR motoneuron pools. This suggests that some of these neurons may be responsible for controlling both muscles.

Animals↗
PubMed1999

Signal processing related to the vestibulo-ocular reflex during combined angular rotation and linear translation of the head.

The contributions of vestibular nerve afferents and central vestibular pathways to the angular (AVOR) and linear (LVOR) vestibulo-ocular reflex were studied in squirrel monkeys during fixation of near and far targets. Irregular vestibular afferents did not appear to be necessary for the LVOR, since when they were selectively silenced with galvanic currents the LVOR was essentially unaffected during both far- and near-target viewing. The linear translation signals generated by secondary AVOR neurons in the vestibular nuclei were, on average, in phase with head velocity, inversely related to viewing distance, and were nearly as strong as AVOR-related signals. We suggest that spatial-temporal transformation of linear head translation signals to angular eye velocity commands is accomplished primarily by the addition of viewing distance multiplied, centrally integrated, otolith regular afferent signals to angular VOR pathways.

Afferent Pathways↗
PubMed2003

Signal processing of semicircular canal and otolith signals in the vestibular nuclei during passive and active head movements.

The vestibular nerve sends signals to the brain that code the movement and position of the head in space. These signals are used by the brain for a variety of functions, including the control of reflex and voluntary movements and the construction of a sense of self-motion. If many of these functions are to be carried out, a distinction must be made between sensory vestibular signals related to active head movements and those related to passive head movements. Current evidence is that the distinction occurs at an early stage of sensory processing in the brain, and the results are evident in the firing behavior of neurons in the vestibular nuclei that receive direct inputs from the vestibular nerve. Several specific examples of how sensory information related to passive and active head movements is transformed in the vestibular nuclei are discussed.

Animals↗
PubMed1984

Simulation of vestibular semicircular canal responses during righting movements of a freely falling cat.

The righting maneuver of a freely falling cat was filmed at 1000 pictures per second, and the head position about the roll axis was digitized from each film frame using a graphics input tablet. The head angular velocity and acceleration were computed from the roll axis position trajectory. Head acceleration trajectories approximated two periods of a damped sinusoid at a frequency of 26 Hz. Head acceleration peak amplitudes exceeded 120,000 deg/s2. These trajectories were used as stimuli for the horizontal semicircular canals in a computer simulation of first-order afferent responses during the fall. Linear system afferent response dynamics, characterized in a previous study of the cat horizontal canal using pseudorandom rotations, provided the basis for linear predictions of falling cat afferent responses. Results showed predicted single afferent firing rates that exceeded physiological values; and variations in afferent sensitivities and phase were predicted among different neurons. Fast head movement information could be carried by ensemble populations of vestibular neurons, and a phase-locking encoding hypothesis is proposed which accomplishes this. Implications for central program versus peripheral vestibular feedback strategies for motor control during falling are presented and discussed.

Afferent Pathways↗
PubMed1999

Linear vestibular self-motion signals in monkey medial superior temporal area.

The present study was aimed at investigating the sensitivity to linear vestibular stimulation of neurons in the medial superior temporal area (MST) of the macaque monkey. Two monkeys were moved on a parallel swing while single-unit activity was recorded. About one-half of the cells (28/51) responded in the dark either to forward motion (n = 10), or to backward motion (n = 11), or to both (n = 7). Twenty cells responding to vestibular stimulation in darkness were also tested for their responses to optic flow stimulation simulating forward and backward self-motion. Forty-five percent (9/20) of them preferred the same self-motion directions, that is, combined visual and vestibular signals in a synergistic manner. Thirty percent (6/20) of the cells were not responsive to visual stimulation alone. The remaining 25% (5/20) preferred directions that were antialigned. Our results provide strong evidence that neurons in the MST area are at least in part involved in the processing of self-motion.

Animals↗
PubMed1990

Vestibular evoked potentials with short and middle latencies recorded in humans.

Following success in recording short latency vestibular evoked potentials in experimental animals, we have succeeded in our attempts to record such potentials in human subjects. The stimuli were repetitive, short steps of high intensity angular acceleration (10,000 degrees/sec2) with short rise times which would synchronously activate many neurons of the vestibular pathway. Stringent control procedures ensured that the recorded activity was not an artefact. Short latency vestibular evoked potentials were recorded in 10 normal subjects with peak latencies of 3.5, 6.0 and 8.4 msec and amplitudes of 0.5 microV. Middle latency potentials were also recorded with latencies of 8.8, 18.8 and 26.8 msec and amplitudes of 15 microV. These responses were absent in a cadaver and in patients with bilateral dead labyrinths. In normal subjects, these vestibular evoked potentials were not affected by white noise. In conclusion, short and middle latency vestibular evoked potentials were recorded in normal human subjects.

Adolescent↗
PubMed2002

Inner ear pathology in the mucopolysaccharidosis VII mouse.

Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is caused by dysfunction of the acid hydrolase beta-D-glucuronidase. The defect results in the accumulation of incompletely degraded glycosaminoglycans within lysosomes of a wide array of cell types. MPS VII is associated with mixed (conductive and sensorineural) hearing loss, vision defects, shortened stature, mental retardation and decreased lifespan. Whether the sensorineural component of hearing loss in MPS VII involves degeneration of cochlear sensory cells is not yet clear. The MPS VII mouse resembles its human counterpart in all major aspects, and has been the focus of extensive research seeking to correct MPS VII and other lysosomal storage diseases. The value of potential treatments for this hearing loss can be determined only if cochlear pathology in this model is well characterized. We examined threshold sensitivity, frequency tuning, hair cell density and the appearance of the cochlea and vestibular organs in MPS VII mice ranging from 1.0 to 7.5 months of age. At all ages, lysosomal storage is pronounced within cells of spiral limbus, spiral prominence, spiral ligament and glial cells, but not within organ of Corti, stria vascularis, or neurons. Within the vestibular maculae and cristae, both hair cells and supporting cells also show lysosomal storage. Although hearing thresholds are never normal, reduction in the sharpness of frequency tuning is not apparent until 2.5 months of age, suggesting that the sensorineural component of hearing loss begins in adulthood. No evidence was found for cell loss within the organ of Corti, or any other structure, however. Our results suggest that sensorineural hearing loss in the MPS VII mouse is not caused by degeneration, but may arise from alterations in mass and stiffness of cochlear structures or impaired sensory cell function. They also indicate a possible vestibular component in MPS VII.

Action Potentials↗
PubMed2004

Probing the human vestibular system with galvanic stimulation.

Galvanic vestibular stimulation (GVS) is a simple, safe, and specific way to elicit vestibular reflexes. Yet, despite a long history, it has only recently found popularity as a research tool and is rarely used clinically. The obstacle to advancing and exploiting GVS is that we cannot interpret the evoked responses with certainty because we do not understand how the stimulus acts as an input to the system. This paper examines the electrophysiology and anatomy of the vestibular organs and the effects of GVS on human balance control and develops a model that explains the observed balance responses. These responses are large and highly organized over all body segments and adapt to postural and balance requirements. To achieve this, neurons in the vestibular nuclei receive convergent signals from all vestibular receptors and somatosensory and cortical inputs. GVS sway responses are affected by other sources of information about balance but can appear as the sum of otolithic and semicircular canal responses. Electrophysiological studies showing similar activation of primary afferents from the otolith organs and canals and their convergence in the vestibular nuclei support this. On the basis of the morphology of the cristae and the alignment of the semicircular canals in the skull, rotational vectors calculated for every mode of GVS agree with the observed sway. However, vector summation of signals from all utricular afferents does not explain the observed sway. Thus we propose the hypothesis that the otolithic component of the balance response originates from only the pars medialis of the utricular macula.

Afferent Pathways↗
PubMed1987

Comparisons of the immunocytochemical localization of choline acetyltransferase in the vestibular nuclei of the monkey and rat.

Immunocytochemical studies of the brainstem were done in the squirrel monkey and rat using the same polyclonal antisera for choline acetyltransferase (ChAT). Cells immunoreactive for ChAT (ChATir) were evident in large numbers in visceral and motor cranial nerve nuclei in both species, but virtually no ChATir cells were seen in the vestibular nuclear complex of the rat. In the monkey ChATir cells were distributed in caudal parts of the medial (MVN) and in dorsal parts of the inferior (IVN) vestibular nuclei. Only a few immunoreactive cells were seen in the rostral MVN and none were found in cell group f of the IVN. Nearly all cells of group z and x, which do not receive primary vestibular afferents, were immunoreactive to ChAT. None of the cells in the superior and lateral vestibular nuclei, cell group y, the infracerebellar nucleus or the interstitial nucleus of the vestibular nerve were immunoreactive for ChAT. Cells immunoreactive to ChAT were present in large numbers in the rostral part of the nucleus prepositus in the monkey, but not in the rat. The relatively small number and distribution of ChATir cells in the MVN suggested they could constitute only a small fraction of the MVN neurons that contribute to a massive commissural system. Significant differences in cholinergic vestibular neurons appear to exist between the rat and the monkey.

Animals↗
PubMed1997

A microcomputer program for automated neuronal spike detection and analysis.

A system for on-line spike detection and analysis based on an IBM PC/AT compatible computer, written in TURBO PASCAL 6.0 and using commercially available analog-to-digital hardware is described here. Spikes are detected by an adaptive threshold which varies as a function of signal mean and its variability. Since the threshold value is determined automatically by the signal-to-noise ratio analysis, the user is not actively involved in controlling its level. This program has been reliably used for the detection and analysis of the spike discharge of vestibular system afferent neurons. It generates the interval-joint distribution graph, the interval histogram, the autocorrelation function, the autocorrelation histogram, and phase-space graphs, thus, providing a complete set of graphical and statistical data for the characterization of the dynamics of neuronal spike activity. Data can be exported to other software such as Excel, Sigmaplot and MatLab, for example.

Ambystoma↗
PubMed1982

Spinal cord development in anuran larvae: II. Ascending and descending pathways.

The ontogeny of ascending and descending spinal pathways was examined in bullfrog (Rana catesbeiana) tadpoles using the transported histochemical marker, horseradish peroxidase (HRP). The adult pattern of brainstem projections to lumbar spinal cord is evident as early as larval stage I (Taylor and Kollros, Anat. Rec., 94:7-24, 1946), although the number and size of projecting cells increases as the animal matures. These projections arise from presumptive hypothalamic neurons at the diencephalic-mesencephalic border as well as from neurons of the vestibular nucleus, oculomotor nucleus, and reticular formation. In contrast to the stability of the pattern of descending projections, the sources of fibers ascending to the brainstem change during larval life. In early larval stages, brainstem projections from lumbar spinal cord arise primarily from Rohon-Beard cells and neurons of the superficial dorsal horn. In later stages, neurons in the intermediate and ventral areas of the spinal gray can also be retrogradely labeled by HRP application to the brainstem at the level of the VIIIth nerve. Evidence of the existence of dorsal column and lateral cervical nuclei in adult frog and tadpoles older than stage VIII is presented. The ascending projections of embryonically born primary neurons were also investigated. Rohon-Beard cells, which are sensory neurons with their cell bodies in the spinal cord, were found to send ascending processes as least as far rostral as the level of the VIIIth nerve entry zone. Anterolateral and dorsal marginal cells, probable homologs, respectively, of mammalian spinal border cells and cells of Waldeyer (1888), were also found to project rostrally at least to the rhombencephalon. These marginal cells persisted through metamorphosis into adulthood.

Afferent Pathways↗
PubMed2006

Extraretinal signals in MSTd neurons related to volitional smooth pursuit.

Smooth pursuit (SP)-related neurons in the dorsal-medial part of medial superior temporal cortex (MSTd) carry extraretinal signals that may play a role in maintenance of SP once eye velocity matches target velocity. For example, it has not been determined whether the extraretinal signals reflect volitional SP commands or proprioception. The aim of this study was to test some potential sources of extraretinal signals in MSTd pursuit neurons. We tested 40 MSTd neurons during step-ramp SP with target blink conditions to show that they carried an extraretinal signal. To examine potential contributions from eye movements that might reflect proprioceptive feedback from eye muscles, we tested MSTd neurons during rotational vestibular ocular reflex in complete darkness (VORd). Vestibular stimulation was delivered in the earth horizontal plane to elicit reflex driven smooth eye movements that matched the speed and frequency of volitional SP. We also tested VOR in the light (VOR x 1) and cancellation of the VOR (VOR x 0). Our neurons were modulated during both SP and cancellation of the VOR. In contrast, MSTd smooth pursuit neurons with extraretinal signals were not significantly modulated during VORd (sensitivity < or = 0.10 spike/s/ degrees /s). This combination of properties is compatible with classifying these neurons as gaze-velocity related. Absence of modulation during VORd testing could be caused by cancellation of head and eye movement sensitivity or dependence of neuronal firing on volitional SP commands. Our results support the suggestion that modulation of SP-related MSTd neurons reflects volitional SP commands rather then eye movements generated by reflex pathways.

Animals↗
PubMed2003

Vestibular nucleus projections to the Edinger-Westphal and anteromedian nuclei of rabbits.

The Edinger-Westphal nucleus (EW), anteromedian nucleus (AM) and adjacent neurons in the ventral tegmental area (VTA) are sources of preganglionic parasympathetic innervation of intraocular smooth muscle, including blood vessels, pupillary muscle and the ciliary body in mammals. They also have central connections that are believed to affect parasympathetic outflow indirectly. This study utilized anterograde transport of biotinylated dextran amine and Phaseolus vulgaris leucoagglutinin to demonstrate direct projections from the vestibular nuclei to the Edinger-Westphal and anteromedian nuclei in rabbits. The rabbit AM and adjacent VTA contain moderate to intensely choline acetyltransferase (ChAT)-immunopositive neurons. The rabbit EW, by contrast, is nearly devoid of ChAT-immunopositive neurons. Vestibular nucleus projections to these regions originate from all levels of the superior, medial and lateral vestibular nuclei, but do show topographic organization. The densest terminations were observed in AM and the ventral and central aspects of EW. The projections to AM terminate in both ipsilaterally and in a narrow paramedian region. Predominantly ipsilateral terminations were observed in VTA. Terminations on ChAT-positive cells in AM and VTA were verified in three rabbits. It is suggested that projections to some intensely ChAT-positive AM and VTA neurons may be a substrate for vestibular influences on lens accommodation, pupillary constriction and regulation of intraocular circulation during changes in posture and gravitoinertial challenges. The projections to ChAT-negative (and weakly immunoreactive) cells in AM, VTA and EW, on the other hand, are likely to contribute vestibular signals to a variety of motor responses via descending pathways.

Animals↗
PubMed2005

Behavior of the position vestibular pause (PVP) interneurons of the vestibuloocular reflex during head-free gaze shifts in the monkey.

Most behavioral studies indicate that the efficacy (gain) of the vestibuloocular reflex (VOR) in primates is modulated during the voluntary head movements that accompany large shifts in the direction of gaze. However, the timing and degree of this modulation is the subject of some debate. The neurophysiological substrate for this apparent gain reduction has been sought in the behavior of the type I position vestibular pause (PVP) neuron, a well-known type of interneuron in the direct VOR pathway. With the head fixed, PVPs increase their firing rates with contraversive eye position and with ipsiversive passive head rotation and also cease firing (pause) for the duration of ipsiversive saccades. During head-free ipsiversive gaze shifts, the eyes and head move in the same direction. If the vestibular signal carried by PVPs provides the primary drive for the VOR, the vestibular signal should be present during ipsiversive gaze shifts to the degree that the VOR is present. Of 25 type I PVPs recorded, 21 ceased their discharge for the entire duration of the rapid, eye-saccade component of an ipsiversive gaze shift. The resumption of activity occurred, on average, 13 ms after the end of the saccade. These results suggest that the activity of the vast majority of PVP neurons do not reflect the state of the VOR, but rather PVPs are completely eliminated from participation in the reflex during head-free gaze movements. We conclude that if any modulation of the VOR does exist, it must occur through other, probably longer-latency, pathways.

Action Potentials↗
PubMed1989

Electrophysiological study of the tangential vestibular nucleus of the chick embryo "in vitro".

The two main neuron types of the tangential vestibular nucleus, the principal and the elongate cells, were investigated using intracellular recordings on brain slice preparations of 15-16 day chick embryos. Their identification was confirmed by intracellular injections of the fluorescent dye, Lucifer yellow. The passive membrane properties of these two neuron types were not sufficient criteria for their identification, whereas their responses to current pulse injections were distinctive. The elongate cells showed a nonlinear current-voltage relationship to hyperpolarizing currents and they fired repetitively at high frequencies without accommodation when the cells were depolarized. Neither of these two properties were observed in principal cells. Synaptic responses to vestibular nerve stimulation were different for the two neurons. The elongate cells responded gradually to increasing stimulus intensity, while the principal cells exhibited two clear postsynaptic responses: a low-threshold action potential initiated by an all-or-none EPSP, and a second, higher threshold, longer latency and graded EPSP. The latter EPSP is characterized by a slow rise time and a long duration. The findings obtained at this embryonic age are consistent with data concerning principal and elongate cell innervation by different caliber fibers comprising the vestibular nerve. The early EPSP recorded from the principal cells is attributed to the colossal fibers, which are vestibular afferents of large diameter forming calyciform contacts, the spoon endings, exclusively on the principal cells. The other synaptic responses recorded from the elongate and principal cells are due to the firing of different classes of small vestibular afferents. These experiments were performed in this new preparation at a critical age for the development of the spoon endings.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗