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PubMed1993

Morphological changes in rat vestibular system following weightlessness.

Mammalian gravity receptors (maculas) are morphologically organized for weighted, parallel distributed processing of information. There are two basic circuits: 1) highly channeled, type I cell to calyx; and 2) distributed modifying, type II cells to calyces and processes. The latter circuit should be the more adaptable since it modifies final output. To test this hypothesis, rats were flown in microgravity for 9 days aboard a space shuttle and euthanized shortly after landing. Hair cells and ribbon synapses from maculas of 3 flight and 3 ground control rats were studied ultrastructurally in blocks of 50 serial sections. Synapses increased by approximately 41% in type I cells and by approximately 55% in type II cells in flight animals. There was a shift toward the spherular form of ribbon synapse in both types of hair cells in flight animals (P < or = 0.0001), a near doubling of pairs in the flight rats (P < or = 0.0001), and an increase, by a factor of 12, in groups of synapses in type II cells (P < or = 0.0001). Current findings tend to support the stated hypothesis and indicate that mature utricular hair cells retain synaptic plasticity, permitting adaptation to an altered gravitational environment.

Acoustic Maculae↗
PubMed1993

Neurophysiology of the nodulofloccular system.

The nodulofloccular lobe is the phylogenetically oldest part of the cerebellum. The nodulus is divided into 6 zones and the flocculus into 7 zones, each of which receives ascending fiber projections from a small region of the inferior olive and which projects Purkinje cell axons to a small group of cerebellar or vestibular nuclear neurons. This zonal structure is a basis of crucial importance for understanding the complex functional involvement of the nodulofloccular system. The best studied is the H zone of the flocculus which receives horizontal retinal slip signals through climbing fibers and which projects to relay cells of the horizontal vestibulocular reflex (VOR). The flocculus hypothesis of VOR control proposes that the H zone adaptively controls the gain of the horizontal vestibuloocular reflex by referring to retinal errors, and has been supported by lesion experiments and recording from Purkinje cells and also by theoretical modeling of the flocculo-oculomotor system.

Cerebellum↗
PubMed1994

Intracellular calcium signals are enhanced for days after Pavlovian conditioning.

Previous observations have implicated GABA as a neurotransmitter released by the vestibular sensory neurons ("hair cells") of the snail Hermissenda onto visual sensory neurons, the type B cells, whose cell bodies are the sites of biophysical and biochemical changes during and following Pavlovian conditioning. Still other observations demonstrated that light-GABA pairings that simulate stimuli presented during Pavlovian conditioning cause prolonged elevation of intracellular Ca2+ and transformation of GABA-induced synaptic inhibition into excitation. Intracellular Ca2+ signals in response to GABA perfused onto the postsynaptic type B terminal branches are shown here to be prolonged on days after conditioning, but not after control paradigms. These and past results demonstrate two separate sites, i.e., the cell body and the terminal branches, for learning-induced changes after Pavlovian conditioning.

Animals↗
PubMed2000

A role for chloride in the hyperpolarizing effect of acetylcholine in isolated frog vestibular hair cells.

Acetylcholine (ACh) is the dominant transmitter released from inner ear efferent neurons. In frog vestibular organs, these efferent neurons synapse exclusively with type II hair cells. Hair cells isolated from the frog saccule hyperpolarize following the application of 50 microM ACh, thereby demonstrating the presence of an ACh receptor. A role for Cl(-) in the response of hair cell-bearing organs to efferent nerve activation or ACh application was suggested some years ago. Perfusion with solutions in which most of the Cl(-) was replaced by large impermeant anions decreased the cholinergic inhibition of afferent firing in the cat and turtle cochleas, and frog semicircular canal. Our previous work in the intact organ demonstrated that substitution of large impermeant anions for Cl(-) or use of Cl(-) channel blockers reduced the effect of ACh on saccular afferent firing. Using the perforated-patch clamping technique, replacement of Cl(-) by methanesulfonate, iodide, nitrate, or thiocyanate attenuated the hyperpolarizing response to ACh in hair cells isolated from the frog saccule. The chloride channel blockers picrotoxin and 4,4'-dinitrostilbene-2,2'-disulfonic acid were also tested and found to inhibit the ACh response. Thus, the present work demonstrates that the effects of Cl(-) substitutions or Cl(-) channel blockers on the ACh response in the intact saccule can be explained completely by effects on the hair cell. Evidence is also presented for the presence of the messenger RNA for a calcium-dependent chloride channel in all hair cells but especially saccular hair cells. This channel may be involved in the response to ACh. The precise role for chloride in this response, whether as a distinct ion current, as a transported ion, or as a permissive ion for other components, is discussed.

Acetylcholine↗
PubMed1995

Effect of vestibular nerve section on cytochrome oxidase activity in the vestibular ganglion cells of the squirrel monkey.

Cytochrome oxidase (CO) activity of the vestibular ganglion cells of the squirrel monkey was demonstrated histochemically under normal and experimental conditions. Under general anesthesia, right vestibular nerve section was performed on adult squirrel monkeys between the vestibular ganglion and brain stem. The left side was left intact and was used as a within-animal normal control. One squirrel monkey that did not undergo vestibular nerve section was also included in the normal group. Following a survival period of seven months, neurons in the vestibular ganglion of both sides were examined. In the normal control sides, a significant negative correlation between the size of the neuron and its optical density for CO stain was observed. Many neurons in the vestibular ganglion survived after vestibular nerve section, but their cell sizes and optical densities of CO stain decreased compared with those of the control side.

Animals↗
PubMed1980

Vestibular responses and branching of interstitiospinal neurons.

1. Interstitiospinal neurons were activated by antidromic stimulation of the ventromedial funiculus of the spinal cord at C1 and C4 in cerebellectomized cats under chloralose anesthesia. 46% of these neurons responded only at C1 (N cells) and the remaining 54% responded at C4 also (D cells). There is no topographical difference in the location of N and D cells. Conduction velocities of N cells were significantly slower than those of D cells. 2. Stimulation of the contralateral whole vestibular nerve evoked firing of 31% of both N and D cells; some responded early enough to suggest disynaptic connections, many responded late. Stimulation of the ipsilateral whole vestibular nerve evoked firing of several cells, one spontaneously discharging D cell was inhibited. 3. Stimulation of the contralateral individual semicircular canal nerves evoked firing of 33% of N cells and 13% of D cells. Most of these responses were late. N cells responded not only to the vertical canals but also to the horizontal canal, whereas D cells responded to the horizontal canal, but seldom to the vertical ones. Most canal responding neurons received specific input, only two N cells received convergent input from both the anterior and horizontal canals. Stimulation of the ipsilateral canals did not evoke excitation of any cells tested; one D cell was inhibited by stimulation of the horizontal canal nerve. 4. Stimulation of the rostral medial vestibular nucleus evoked characteristic negative field potentials centered in the contralateral interstitial nucleus of Cajal (INC). Approximately 60% of both N and D cells received excitation from the contralateral vestibular nuclei. About 17% of these responding neurons received monosynaptic excitation, most frequently from the rostral medial nucleus. Stimulation of the ipsilateral vestibular nuclei evoked firing of 12% of both N and D cells. 5. Twenty-nine neurons were fired antidromically by weak stimuli applied to the ipsilateral vestibular nuclei. Twenty-seven of the 29 were activated only from C1 and were found in the INC (10 cells) and in the reticular formation dorsal to the INC (19 cells). Measurement of the spread of the effect of stimulus current and comparison of latencies to stimulation of the vestibular nuclei and C1 indicated that these neurons have axon collaterals going to the ipsilateral vestibular nuclei. Only one of them received excitation from the contralateral posterior canal, others did not respond to the labyrinth. Some were activated by stimulation of the vestibular nuclei.

Animals↗
PubMed1985

Afferents to the flocculus of the cerebellum in the rhesus macaque as revealed by retrograde transport of horseradish peroxidase.

To investigate the afferent projections to the flocculus in a nonhuman primate, we injected horseradish peroxidase into one flocculus of six rhesus macaques (Macaca mulatta) and processed their brains according to the tetramethylbenzidine protocol to reveal retrogradely labeled neurons. Labeled neurons were found in a large set of nuclei within the rostral medulla and the pons. The greatest numbers of labeled neurons were in the vestibular complex and the nucleus prepositus hypoglossi. There were neurons labeled bilaterally throughout all the vestibular nuclei except the lateral vestibular nucleus, but most of the labeled neurons were in the caudal parts of the medial and inferior vestibular nuclei and in the central part of the superior vestibular nucleus; the nucleus prepositus was also labeled bilaterally, primarily caudally. Modest numbers of labeled neurons were found in the y-group, most ipsilaterally, and many neurons were labeled in the interstitial nucleus of the vestibular nerve. No labeled neurons were found in the vestibular ganglion following a large injection into the flocculus. A second large source of afferents to the flocculus was the medial, paramedial, and raphe reticular formation. Dense aggregates of labeled neurons were located in several pararaphe nuclei of the rostral medulla and the rostral pons and in the nucleus reticularis paramedianus of the medulla and several component nuclei of the nucleus reticularis tegmenti pontis bilaterally. Several groups of cells within and abutting upon the medial and rostral aspects of the abducens nucleus were labeled bilaterally. There was a modest projection from two parts of the pontine nuclei. Both a dorsal midline nucleus ventral to the nucleus reticularis tegmenti pontis and a collection of nuclei in a laminar region adjacent to the contralateral middle cerebellar peduncle contained labeled neurons whose numbers, while modest, were large compared to the projections to the flocculus in other animals. This generic difference may be due to the greater development of the smooth pursuit system in monkeys and the consequent need for a more substantial input from the cerebral cortex. As in other genera, the inferior olive projected to the flocculus via the dorsal cap of Kooy and the contiguous ventrolateral outgrowth. The projection was completely crossed and large injections labeled virtually every neuron in the dorsal cap, suggesting that the dorsal cap is the principal source of climbing fiber afferents.(ABSTRACT TRUNCATED AT 400 WORDS)

Abducens Nerve↗
PubMed1993

Heterotopic transplantation of presumptive placodal ectoderm changes the fate of sensory neuron precursors.

The placode-derived cranial sensory neurons of the vestibular and nodose ganglia in avian embryos exhibit differences in neurite growth rate and the duration of neurotrophin-independent survival in vitro that arise prior to gangliogenesis and target contact (Davies, A. M. (1989) Nature 337, 553-555; Vogel, K. S. and Davies, A. M. (1991) Neuron 7, 819-830). To ascertain the state of commitment of presumptive placodal ectoderm to differentiate into neurons of the vestibular or nodose type, we performed heterotopic transplantation of labelled presumptive placodal ectoderm at E1.5 in the chicken embryo. We then assayed transplant-derived neurons for hindbrain innervation patterns, neurite growth and survival at E3.5. We show that presumptive placodal ectoderm is not determined to give rise to neurons of the vestibular or nodose phenotype at E1.5. Explantation of presumptive placodal ectoderm at E1.5 showed that this ectoderm is also not specified to differentiate into neurons at this stage. In addition, we demonstrate that non-neurogenic ectoderm from the trunk can give rise to nodose-type neurons when transplanted heterotopically to the nodose region.

Animals↗
PubMed1999

Survival of chronically-injured neurons can be prolonged by treatment with neurotrophic factors.

Axonal regeneration by chronically-injured supraspinal neurons can be enhanced by neurotrophic factor treatment at the site of injury, although the number of regenerating neurons decreases as the interval between spinal cord injury and treatment increases. This study investigated whether this decline in regenerative response could be due to continued loss of neurons during the post-injury period. Adult rats received a cervical hemisection lesion and axotomized neurons were labeled by retrograde transport of True Blue from the lesion site. Animals were killed one, four or eight weeks after injury and surviving neurons (True Blue-labeled) were counted in the red nucleus and lateral vestibular nucleus. The neuron number in the lateral vestibular nucleus was stable for eight weeks after spinal cord injury, while survival in the red nucleus decreased by 25% between four and eight weeks. To test how neurons respond to a second injury with or without trophic factor treatment, at four, eight, 14 or 22 weeks after injury the lesion cavity was enlarged by 0.5 mm in a rostral direction. Gel foam saturated with ciliary neurotrophic factor, brain-derived neurotrophic factor or basic fibroblast growth factor was placed into the cavity. Animals were killed four weeks later. Re-injury of the spinal cord caused a significant decrease in neuron survival in both the red nucleus and lateral vestibular nucleus, the effects of which were lessened by treatment with ciliary neurotrophic factor or brain-derived neurotrophic factor for the red nucleus and with ciliary neurotrophic factor for the lateral vestibular nucleus, when re-injured at four or eight weeks. Basic fibroblast growth factor did not affect neuron survival at any time post-injury. Ciliary neurotrophic factor was not effective with longer delays (14 or 22 weeks) between the initial injury and re-injury. These results indicate a delayed pattern of secondary neuronal cell loss after spinal cord injury that is exaggerated by re-injury, but which can be ameliorated by treatment with neurotrophic factors.

Animals↗
PubMed1987

Integration of cortical and peripheral information in the lateral vestibular nucleus in the cat.

Neuronal discharges in the lateral vestibular nucleus (LVN) of the cat were studied during stimulation of a forelimb muscle and of a site in the contralateral motor cortex (area 4) capable of activating the same muscle. About one third of the LVN units were reactive to both stimulations or at least responded to one (cortex or muscle) but modified the response pattern when the other was stimulated also. The patterns evoked by a muscle were mostly enhanced on simultaneous stimulation of the cortical zone controlling the same muscle and vice versa. Only in the dorsal division the excitatory responses to muscle stimulation were depressed by simultaneous cortical stimulation. Some functional implications are proposed.

Afferent Pathways↗
PubMed1986

Afferents to the abducens nucleus in the monkey and cat.

The abducens nucleus is a central coordinating element in the generation of conjugate horizontal eye movements. As such, it should receive and combine information relevant to visual fixation, saccadic eye movements, and smooth eye movements evoked by vestibular and visual stimuli. To reveal possible sources of these signals, we retrogradely labeled the afferents to the abducens nucleus by electrophoretically injecting horseradish peroxidase into an abducens nucleus in four monkeys and two cats. The histologic material was processed by the tetramethyl benzidine (TMB) method of Mesulam. In both species the largest source of afferents to the abducens nucleus was bilateral projections from the ventrolateral vestibular nucleus and the rostral pole of the medial vestibular nucleus. Scattered neurons were also labeled in the middle and caudal levels of the medial vestibular nucleus. Large numbers of neurons were labeled in the ventral margin of the nucleus prepositus hypoglossi in the cat and in the common margin of the nucleus prepositus and the medial vestibular nucleus in the monkey, a region we call the marginal zone. Substantial numbers of retrogradely labeled neurons were found in the dorsomedial pontine reticular formation both caudal and rostral to the abducens nuclei. In the monkey, large numbers of labeled neurons were present in the contralateral medial rectus subdivision of the oculomotor complex, while smaller numbers occurred in the ipsilateral medial rectus subdivision and elsewhere in the oculomotor complex. In the cat, large numbers of retrogradely labeled cells were present in a small periaqueductal gray nucleus immediately dorsal to the caudal pole of the oculomotor complex, and a few labeled neurons were also dispersed through the caudal part of the oculomotor complex. Occasional labeled neurons were present in the contralateral superior colliculus in both species. The size and distribution of the labeled neurons within the intermediate gray differed dramatically in the two species. In the cat, the retrogradely labeled neurons were very large and occurred predominantly in the central region of the colliculus, while in the monkey, they were small to intermediate in size and were distributed more uniformly within the middle gray. Among the afferent populations present in the monkey, but not in the cat, was a group of scattered neurons in the ipsilateral rostral interstitial nucleus of the medial longitudinal fasciculus and a denser, bilateral population in the interstitial nucleus of Cajal.(ABSTRACT TRUNCATED AT 400 WORDS)

Abducens Nerve↗