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Optimal firing rate estimation.

We define a measure for evaluating the quality of a predictive model of the behavior of a spiking neuron. This measure, information gain per spike (Is), indicates how much more information is provided by the model than if the prediction were made by specifying the neuron's average firing rate over the same time period. We apply a maximum Is criterion to optimize the performance of Gaussian smoothing filters for estimating neural firing rates. With data from bullfrog vestibular semicircular canal neurons and data from simulated integrate-and-fire neurons, the optimal bandwidth for firing rate estimation is typically similar to the average firing rate. Precise timing and average rate models are limiting cases that perform poorly. We estimate that bullfrog semicircular canal sensory neurons transmit in the order of 1 bit of stimulus-related information per spike.

Action Potentials↗

Nitric oxide synthase localized in a subpopulation of vestibular efferents with NADPH diaphorase histochemistry and nitric oxide synthase immunohistochemistry.

Efferent innervation of the vestibular labyrinth is known to be cholinergic. More recent studies have also demonstrated the presence of the neuropeptide calcitonin gene-related peptide in this system. Nitric oxide is one of a new class of neurotransmitters, the gaseous transmitters. It acts as a second messenger and neurotransmitter in diverse physiological systems. We decided to investigate the anatomical distribution of the synthetic enzyme for nitric oxide, nitric oxide synthase (NOS), to clarify the role of nitric oxide in the vestibular periphery. NADPH diaphorase histochemical and NOS I immunohistochemical studies were done in the adult chinchilla and rat vestibular brainstem; diaphorase histochemistry was done in the chinchilla periphery. Retrograde tracing studies to verify the presence of NOS in brainstem efferent neurons were performed in young chinchillas. Our light microscopic results show that NOS I, as defined mainly by the presence of NADPH diaphorase, is present in a subpopulation of both brainstem efferent neurons and peripheral vestibular efferent boutons. Our ultrastructural results confirm these findings in the periphery. NADPH diaphorase is also present in a subpopulation of type I hair cells, suggesting that nitric oxide might be produced in and act locally upon these cells and other elements in the sensory epithelium. A hypothesis about how nitric oxide is produced in the vestibular periphery and how it may interact with other elements in the vestibular sensory apparatus is presented in the discussion.

Animals↗

Distribution of acetylcholine and catecholamine neurons in the cat brainstem: a choline acetyltransferase and tyrosine hydroxylase immunohistochemical study.

The distribution of acetylcholine neurons in the brainstem of the cat was studied by choline acetyltransferase (ChAT) immunohistochemistry and compared to that of catecholamine neurons examined in the same or adjacent sections by tyrosine hydroxylase (TH) immunohistochemistry. The largest group of ChAT-positive (+) neurons was located in the lateral pontomesencephalic tegmentum within the pedunculopontine tegmental nucleus and the laterodorsal tegmental nucleus rostrally and within the parabrachial nuclei and locus coeruleus nucleus more caudally. TH+ neurons were found to be coextensive and intermingled with ChAT+ neurons in the dorsolateral pontomesencephalic tegmentum, where the number of ChAT+ cells (approximately 18,500) exceeded that of the TH+ cells (approximately 12,000). In the caudal pons, scattered ChAT+ neurons were situated in the ventrolateral tegmentum together with TH+ neurons. In the medulla, numerous ChAT+ cells were located in the lateral tegmental field, where they extended in a radial column from the dorsal motor nucleus of the vagus to the ventrolateral tegmentum around the facial and ambiguus nuclei, occupying the position of preganglionic parasympathetic neurons of the 7th, 9th, and 10th cranial nerves. TH+ cells were also present in this field. Neurons within the general visceral, special visceral, and somatic motor cranial nerve nuclei were all immunoreactive to ChAT. Scattered ChAT+ neurons were also present within the medullary gigantocellular and magnocellular tegmental fields together with a small number of TH+ neurons. Other groups of ChAT+ cells were identified within the periolivary nuclei, parabigeminal nucleus, prepositus hypoglossi nucleus, and the medial and inferior vestibular nuclei. Acetylcholine neurons thus constitute a heterogeneous population of cells in the brainstem, which in addition to including the somatic and visceral efferent systems, comprises many other discrete systems and represents an important component of the brainstem reticular formation. The proximity to and interdigitation with catecholamine neurons within these systems may be of important functional significance.

Acetylcholine↗

Direct excitatory and inhibitory synaptic inputs from the medial mesodiencephalic junction to motoneurons innervating extraocular oblique muscles in the cat.

This study investigated the nature of synaptic inputs from the Forel's field H (FFH) in the medial mesodiencephalic junction to inferior oblique (IO) motoneurons in the oculomotor nucleus and superior oblique (SO) motoneurons in the trochlear nucleus in anesthetized cats, using intracellular recording techniques. Stimulation of the FFH induced monosynaptic EPSPs in IO motoneurons on both sides. Paired stimulation of the ipsilateral FFH and contralateral vestibular nerve substantiated that the FFH-induced EPSPs were caused mainly by direct excitatory fibers from the FFH to IO motoneurons and partly by axon collaterals of excitatory neurons in the vestibular nuclei. Among parts of the FFH, the medial part was most effective for producing the EPSPs. Systematic tracking with the stimulating electrode in and around the FFH revealed that effective sites of stimulation inducing negative field potentials in the IO subdivision of the oculomotor nucleus, identified as extracellular counterparts of the EPSPs in IO motoneurons, were also located in the interstitial nucleus of Cajal, nearby reticular formation and posterior commissure, besides within and near the medial part of the FFH. Areas far rostral, dorsal and ventral to the FFH were ineffective. EPSP-IPSPs or EPSPs were mainly induced in SO motoneurons on both sides by FFH stimulation. Latencies of these EPSPs and IPSPs were close to those of the EPSPs in IO motoneurons, indicating their monosynaptic nature. Effective stimulation sites for inducing these synaptic potentials overlapped those for the EPSPs in IO motoneurons. Based on these results, it was suggested that excitatory and inhibitory premotor neurons directly controlling IO and SO motoneurons were located within and near the medial part of the FFH.

Animals↗

[Vestibular responses of "fast" and "slow" Deiter's nucleus neurons].

The response of vestibulospinal neurons to the tilt in the frontal plane was studied in decerebrate cats. The neurons were identified antidromically by L1 stimulation. The response to the tilt was found to be correlated with the speed of axonal conductance: the neurons responding to the ipsilateral tilt had the latency of the antidromic response 2.8 +/- 0.7 ms, while those responding to the contralateral tilt--4.6 +/- 2.0 ms.

Animals↗

The GABAergic cerebello-olivary projection in the rat.

Immunocytochemical detection of glutamate decarboxylase (GAD), the predominant biosynthetic enzyme of gamma-aminobutyric acid (GABA), reveals the presence of a dense GABAergic innervation in all parts of the inferior olive. One brain center that provides a substantial projection to the inferior olive is the cerebellar nuclei, which contain many small GABAergic neurons. These neurons were tested as a source of GABAergic olivary afferents by combining retrograde tract tracing with GAD immunocytochemistry. As expected from previous studies, injections of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the inferior olive retrogradely label many small neurons in the interposed and lateral cerebellar nuclei and the dorsal part of the lateral vestibular nucleus, and fewer neurons in the ventro-lateral region of the medial cerebellar nucleus. These projections are predominantly crossed and are topographically arranged. The vast majority, if not all, of these projection neurons are also GAD-positive. The relative contribution of this projection to the GABAergic innervation of the inferior olive was tested by lesion of the cerebellar nuclei, or the superior cerebellar peduncle. Within 10 days the lesion eliminates most GAD-immunoreactive boutons in the principal olive, the rostral lamella of the medial accessory olive, the ventrolateral outgrowth, and the lateral part of the dorsal accessory olive ventral fold. Thus, the effectiveness of this depletion demonstrates that the cerebellar nuclei provide most of the GABAergic innervation to regions of the inferior olive known to receive a cerebellar projection. Moreover, when the lateral vestibular nucleus is damaged, the dorsal fold of the dorsal accessory olive is depleted of GABAergic boutons. The synaptic relations that boutons of the GABAergic cerebello-olivary projection share with olivary neurons were investigated at the electron microscopic level by GAD-immunocytochemistry, anterograde degeneration of the cerebellar axons or anterograde transport of WGA-HRP. All of these methods confirm that GABAergic, cerebello-olivary axon terminals contain pleomorphic vesicles, and synapse on various portions of olivary neurons, and especially on dendritic spines within glomeruli, often in very close proximity to the gap junctions that characteristically couple the dendritic profiles. These results demonstrate four major points: that virtually all of the GABAergic, and presumably inhibitory, neurons of the cerebellar and dorsal lateral vestibular nuclei are projection neurons; that a large portion of the inferior olive receives GABAergic afferents from the cerebellar nuclei; that a portion of the dorsal accessory olive receives GABAergic afferents from the dorsal lateral vestibular nucleus; and that cerebello-olivary fibers often synapse near gap junctions, and therefore could influence electrical coupling of olivary neurons.

Animals↗

Patterns of vestibular and neck responses and their interaction: a comparison between cat cortical neurons and human psychophysics.

The present study provides evidence that during whole-body rotation and during isolated rotation of either the head or the trunk, essentially the same processing of labyrinthine and neck afferent inputs takes place in neurons of the cat's ASS cortex and in humans who try to distinguish these stimulus conditions. This processing includes, among others (1) measurement of angular velocity and displacement during labyrinthine stimulation (whole-body rotation); (2) indication of trunk rotation as well as of an apparent head rotation in the opposite direction during neck stimulation (isolated trunk rotation); and (3) subtraction as well as addition of labyrinthine and neck afferent inputs during combined stimulation (isolated head rotation). Subtraction provides a basis for the discrimination between whole-body rotation and isolated head rotation; addition may optimize the indication of movement and position of the head in space.

Acceleration↗

Pontine reticular origin of cholinergic excitatory afferents to the locus coeruleus controlling the gain of vestibulospinal and cervicospinal reflexes in decerebrate cats.

1. Previous experiments had shown that the medullary inhibitory reticulospinal (mRS) neurons act 180 degrees out-of-phase with respect to the excitatory vestibulospinal (VS) neurons during the vestibular and the neck reflexes involving the limb extensor motoneurons. This finding suggested that the higher the firing rate of the medullary inhibitory RS neurons in the animal at rest, the greater the disinhibition which affects the limb extensor motoneurons during side-down roll tilt of the animal or side-up neck rotation, thus leading to an increased gain of response of limb extensors to sinusoidal stimulation of labyrinth and neck receptors. The gain of these postural reflexes would then represent a sensitive test to evaluate the background discharge of the inhibitory reticulospinal system of the medulla. 2. The discharge of the inhibitory mRS neurons is under the tonic excitatory control of cholinergic pontine reticular formation (pRF) neurons which are also self-excitatory, while these cholinergic pontine neurons are in turn inhibited by the norepinephrine (NE)-containing locus coeruleus (LC) neurons, which are also self-inhibitory due to mechanisms of recurrent and/or lateral inhibition. The present experiments were performed to find out whether cholinergic and cholinoceptive pontine reticular neurons, which are under the inhibitory control of the LC neurons, also send axons to the LC on which they may exert an excitatory influence. This excitatory effect would then counteract the self-inhibitory influence mediated by the NE, which acts on the alpha 2-adrenoceptors distributed on the somatodendritic membrane of the LC neurons. 3. In precollicular decerebrate cats, local injection into the dorsal aspect of the pontine tegmentum of 0.25 microliter of a solution of the muscarinic blocker atropine sulphate at the concentration of 6 micrograms/microliter of sterile saline did neither modify the postural activity in the ipsilateral limbs nor the response gain of the ipsilateral forelimb extensor triceps brachii to sinusoidal stimulation of labyrinth receptors (roll tilt of the animal at 0.15 Hz, +/- 10 degrees). These negative results were attributed to the fact that in these preparations the activity of the cholinergic and cholinoceptive pRF neurons and the related inhibitory mRS neurons is very low, due to the tonic discharge of the NE-containing LC neurons, which exert a prominent inhibitory influence on the underlying reticular structures.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A comparative study of the tangential-oculomotor projection.

Most of the neurons of the tangential vestibular nucleus of birds project to the controlateral oculomotor complex, but it is not known whether there is a homologous projection in mammals. In this study, horseradish peroxidase (HRP) was injected into the oculomotor nucleus of chicks and rabbits, and the distributions of labelled neurons in the target region of the vestibular complex in the two species were compared. In chicks, a large number of labelled neurons formed a continuous band of neurons located in the contralateral tangential, descending and medial nuclei. In rabbits a similar band of labelled neurons was found in the contralateral descending and medial vestibular nuclei, but most of the neurons were caudal to the incoming vestibular nerve fibers, and only a few rostral neurons were located among these fibers. Our results suggest that the tangential nucleus neurons projecting to the oculomotor nucleus may be homologous to the most lateral neurons of the neuronal band of rabbits.

Animals↗

Effect of T2 spinal transection on compensation of horizontal canal related activity in the medial vestibular nucleus following unilateral labyrinth ablation in the decerebrate gerbil.

The effects of spinal transection at T2 upon static and dynamic responses of type I and II neurons in the medial vestibular nucleus after vestibular compensation were investigated in decerebrate Mongolian gerbils (Meriones unguiculatus). Spinal transection in compensated animals resulted in bilaterally depressed spontaneous activity and asymmetry in the response gain of type I neurons, suggesting that tonic spinal inputs contribute to vestibular compensation through effects upon type I neurons.

Adaptation, Physiological↗

Activation of different vestibular subnuclei evokes differential respiratory and pressor responses in the rat.

Activation of the vestibular system can either increase or decrease ventilation. The objectives of the present study were to clarify whether these different responses are the result of activating different vestibular subnuclei, by addressing three questions. Do neurones within the medial, lateral and spinal vestibular nuclei (VN(M), VN(L) and VN(S), respectively) function differently in respiratory modulation? Is the ventral medullary nucleus gigantocellularis (NGC) required to fully express the VN-mediated respiratory responses? Is glutamate, by acting on N-methyl-D-aspartic acid (NMDA) receptors in the vestibular subnuclei, capable of modulating respiration? In anaesthetized, tracheotomized and spontaneously breathing rats, electrical stimuli (< 10 s) applied in the VN(L) and VN(S) significantly elevated ventilation by 35 % and 30 % (P < 0.05), respectively. However, VN(M) stimulation produced statistically significant (P < 0.05) changes that differed depending upon the stimulation site: either ventilatory inhibition (by 40 % in 57 % of the trials) or excitation (by 55 % in 43 % of trials), and which were often accompanied by a pressor response. These electrical-stimulation-evoked cardiorespiratory responses were almost eliminated following microinjection of ibotenic acid into the stimulation sites (P < 0.05) or bilaterally into the NGC (P < 0.05). As compared to vehicle, microinjection of NMDA into the unilateral VN(M), VN(L) and VN(S) significantly increased ventilation to 74 %, 58 % and 60 % (P < 0.05), respectively, with no effect on arterial blood pressure. These data suggest that neurones within the vestibular subnuclei play different roles in cardiorespiratory modulation, and that the integrity of the NGC is essential for the full expression of these VN-mediated responses. The evoked respiratory excitatory responses are probably mediated by glutamate acting on NMDA receptors, whereas the neurotransmitters involved in VN(M)-mediated respiratory inhibition and hypertension remain unknown.

Animals↗

Demonstration of zonal projections from the cerebellar flocculus to vestibular nuclei in monkeys (Macaca fuscata).

Purkinje cells in the flocculus of macaque monkeys were labeled by retrograde axonal transport of horseradish peroxidase from the vestibular nuclei. These neurons are organized in three adjacent, narrow bands which span all folia of the ipsilateral flocculus. The central band, 500-750 micrometer wide, projects to the medial vestibular nucleus, while the two adjacent bands, each 300-500 micrometer wide, innervate the superior vestibular nucleus. These three bands cover about one-half of the total area of the Purkinje cell layer of flocculus. Thus, the pattern of zonal projections in monkeys is the same as reported in rabbits and cats.

Animals↗

Betahistine dihydrochloride treatment facilitates vestibular compensation in the cat.

Unilateral lesion of the vestibular system induces posturo-locomotor deficits that are compensated for with time. Drug therapy is currently used to improve the recovery process and to facilitate vestibular compensation. Betahistine dihydrochloride is an histamine-like substance that has been employed in vestibular pathology; it was found effective in many forms of vertigo and in vestibular-related syndromes. Investigations performed in animal models have shown betahistine-induced neuronal modulations in the vestibular nuclei complex and interactions with the H1 and H3 histamine receptors. Potentially, this substance is therefore capable to interfere with some recovery mechanisms and to improve the behavioral adaptations. But there is at present a total lack of data concerning the influence of betahistine treatment on vestibular compensation in animal models. The aim of this study was to understand the pharmacological activity of betahistine in the restoration of posture and locomotor balance functions in unilateral vestibular neurectomized cats. Posture recovery was assessed by quantifying the surface reaction of the cat's support as measured while standing erect on its four legs, at rest. Locomotor balance recovery was determined using the rotating beam test, by measuring the maximal performance (max. P.) of the cat and its locomotion speed regulation during the postoperative time period. We have compared the recovery profile and time course of these static (posture) and dynamic (equilibrium) functions in three groups of cats. Two experimental groups were treated at daily doses of 50 mg/kg and 100 mg/kg, respectively. Betahistine dihydrochloride was given orally until complete recovery of posturolocomotor functions. One untreated control group served as the reference. Results showed that postoperative treatment strongly accelerated the recovery process in both treated groups, inducing a time benefit of around 2 weeks as compared to the controls. Maximum performance of the cats on the rotating beam as well as locomotion speed regulation were highly correlated to the postoperative development of the cat's support surface, indicating that compensation of the static vestibulospinal deficits conditioned the subsequent locomotor balance recovery. These behavioral data showed that betahistine dihydrochloride constitutes a useful drug therapy for the symptomatic treatment of central vestibular disorders in our animal model of unilateral vestibular lesion. Improvement of vestibular compensation under betahistine postoperative treatment, as evidenced here for the posture and locomotor balance functions, is discussed both in terms of aspecific effect (histamine-induced increase of the level of vigilance) or more direct action in the vestibular nuclei (histamine-induced rebalance of neuronal activity on both sides).

Administration, Oral↗

Physiologic basis for motor learning in the vestibulo-ocular reflex.

The vestibulo-ocular reflex has been used extensively for study of the neural mechanisms of learning that is dependent on an intact cerebellum. Anatomic, physiologic, behavioral, and computational approaches have revealed the neural circuits that are used to generate the vestibulo-ocular reflex and have identified two likely sites of plasticity within those circuits. One site of plasticity is in the vestibular inputs to floccular target neurons, which are located in the vestibular nuclei and receive monosynaptic inhibition from Purkinje cells in the floccular complex of the cerebellar cortex. The other site of plasticity is in the vestibular inputs to Purkinje cells in the floccular complex, possibly in the cerebellar cortex. After reviewing the evidence that supports these conclusions, I consider a number of observations showing that the dynamics of neural circuits or cellular mechanisms play important roles in learning in the vestibulo-ocular reflex.

Fixation, Ocular↗

Postural control in the lamprey: A study with a neuro-mechanical model.

The swimming lamprey normally maintains the dorsal-side-up orientation due to activity of the postural control system driven by vestibular organs. Commands for postural corrections are transmitted from the brain stem to the spinal cord mainly by the reticulospinal (RS) pathways. As shown in previous studies, RS neurons are activated by contralateral roll tilt, they exhibit a strong dynamic response, but much weaker static response. Here we test a hypothesis that decoding of these commands in the spinal cord is based on the subtraction of signals in the left and right RS pathways. In this study, we used a neuro-mechanical model. An intact lamprey was mounted on a platform that restrained its postural activity but allowed lateral locomotor undulations to occur. The activity in the left and right RS pathways was recorded by implanted electrodes. These natural biological signals were then used to control an electrical motor rotating the animal around its longitudinal axis toward the stronger signal. It was found that this "hybrid" system automatically stabilized a normal orientation of the lamprey in the gravitational field. The system compensated for large postural disturbances (lateral tilt up to +/-180 degrees ) due to wide angular zones of the gravitational sensitivity of RS neurons. In the nonswimming lamprey, activity of RS neurons and their vestibular responses were considerably reduced, and the system was not able to stabilize the normal orientation. However, the balance could be restored by imposing small oscillations on the lamprey, which elicited additional activation of the vestibular organs. This finding indicates that head oscillations caused by locomotor movements may contribute to postural stabilization. In addition to postural stabilization, the neuro-mechanical model reproduced a number of postural effects characteristic of the lamprey: 1) unilateral eye illumination elicited a lateral tilt ("dorsal light response") due to a shift of the equilibrium point in the vestibular-driven postural network; 2) removal of one labyrinth resulted in a loss of postural control due to an induced left-right asymmetry in the vestibulo-reticulospinal reflexes, which 3) could be compensated for by asymmetrical visual input. The main conclusion of the present study is that natural supraspinal commands for postural corrections in the roll plane can be effectively decoded on the basis of subtraction of the effects of signals delivered by the left and right RS pathways. Possible mechanisms for this transformation are discussed.

Animals↗

Expression of inorganic phosphate/vesicular glutamate transporters (BNPI/VGLUT1 and DNPI/VGLUT2) in the cerebellum and precerebellar nuclei of the rat.

Expression of inorganic phosphate/vesicular glutamate transporters (BNPI/VGLUT1 and DNPI/VGLUT2) was studied in the cerebellum and precerebellar nuclei of rats using immunohistochemistry and in situ hybridization. DNPI/VGLUT2-stained mossy fibers were principally seen in the vermis (lobules I and VIII-X) and flocculus, whereas BNPI/VGLUT1-stained mossy fibers were localized throughout the cortex. Some vermal and floccular mossy fibers were stained for both transporters. High levels of DNPI/VGLUT2 mRNA hybridization signals were demonstrated in many neurons throughout the vestibular nuclear complex as well as the lateral reticular, external cuneate, inferior olivary and deep cerebellar nuclei. Significant BNPI/VGLUT1 mRNA signals were demonstrated in the lateral reticular nucleus and vestibular nuclear complex but not in the inferior olivary nucleus, indicating that climbing fibers have DNPI/VGLUT2 only. These results show that DNPI/VGLUT2 is expressed preferentially to vestibulo-, reticulo- and cuneocerebellar neurons, some of which also possess BNPI/VGLUT1, suggesting some differential and co-operative functions between DNPI/VGLUT2 and BNPI/VGLUT1 in the cerebellum.

Animals↗