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The brainstem vestibulo-oculomotor pathways are not yet fully known. Three different excitatory tracts could be involved in the transmission of upward vestibular eye movement (VEM) signals and upward eye position (EP) signals to the oculomotor nucleus (III): the medial longitudinal fasciculus (MLF), the brachium conjunctivum (BC), and the crossing ventral tegmental tract (CVTT). The involvement of the MLF pathway originating in the medial vestibular nucleus (MVN) in this transmission is experimentally and clinically well established whereas a role of the BC appears to be questionable. Furthermore, there is now accumulating evidence that the CVTT pathway emerging from the superior vestibular nucleus (SVN) also plays an important role in the mediation of excitatory upward EP and VEM signals to the III. This duplication of pathways (MVN-MLF and SVN-CVTT) could be explained by a supplementary and relatively specific function performed by the SVN-CVTT pathway to counteract the gravity pull in the upward eye movement system. Various arguments in support of this hypothesis are reviewed.

The vestibular portion of the eighth cranial nerve informs the brain about the linear and angular movements of the head in space and the position of the head with respect to gravity. The termination sites of these eighth nerve afferents define the territory of the vestibular nuclei in the brainstem. (There is also a subset of afferents that project directly to the cerebellum.) This chapter reviews the anatomical organization of the vestibular nuclei, and the anatomy of the pathways from the nuclei to various target areas in the brain. The cytoarchitectonics of the vestibular brainstem are discussed, since these features have been used to distinguish the individual nuclei. The neurochemical phenotype of vestibular neurons and pathways are also summarized because the chemical anatomy of the system contributes to its signal-processing capabilities. Similarly, the morphologic features of short-axon local circuit neurons and long-axon cells with extrinsic projections are described in detail, since these structural attributes of the neurons are critical to their functional potential. Finally, the composition and hodology of the afferent and efferent pathways of the vestibular nuclei are discussed. In sum, this chapter reviews the morphology, chemoanatomy, connectivity, and synaptology of the vestibular nuclei.

It has been tacitly assumed that a long descending motor tract axon consists of a private line connecting the cell of origin to a single muscle, as a motoneuron innervates a single muscle. However, this notion of a long descending motor tract referred to as a private line is no longer tenable, since recent studies have showed that axons of all major long descending motor tracts send their axon collaterals to multiple spinal segments, suggesting that they may exert simultaneous influences on different groups of spinal interneurons and motoneurons of multiple muscles. The long descending motor systems are divided into two groups, the medial and the lateral systems including interneurons and motoneurons. In this chapter, we focus mainly on the medial system (vestibulospinal, reticulospinal and tectospinal systems) in relation to movement control of the neck, describe the intraspinal morphologies of single long descending motor tract axons that are stained with intracellular injection of horseradish peroxidase, and provide evidence that single long motor-tract neurons are implicated in the neural implementation of functional synergies for head movements.

Vestibular inputs to the cerebral cortex are important for spatial orientation, body equilibrium, and head and eye movements. We examined vestibular input to the periarcuate cortex in the Japanese monkey by analyzing laminar field potentials evoked by electrical stimulation of the vestibular nerve. Laminar field potential analysis in the depths of the cerebral cortex showed that vestibular-evoked potentials consisted of early-positive and late-negative potentials and early-negative and late-positive potentials in the superficial and deep layers of the periarcuate cortex, respectively, with latencies of 4.8-6.3 ms, suggesting that these potentials were directly conveyed to the cortex through the thalamus. These potentials were distributed continuously in the fundus, dorsal and ventral banks of the spur and the bottom of the junctional part of the arcuate sulcus and spur. This vestibular-projecting area overlapped the cortical distribution of corticovestibular neurons that were retrogradely labeled by tracer injection into the vestibular nuclei (previously reported area 6 pa), and also the distribution of smooth pursuit-related neurons recorded in the periarcuate cortex including area 8 in a trained monkey. These results are discussed in relation to the function of vestibular information in control of smooth pursuit and efferents of the smooth pursuit-related frontal eye field.

Efferents of the flocculus (FL) and ventral paraflocculus (VP) were examined in seven anesthetized Macaca fuscata by anterograde axonal transport method using wheat germ agglutinin-conjugated horseradish peroxidase or phaseolus vulgaris leucoagglutinin. Several major foci of axon terminals were found in the vestibular nuclear complex and cerebellar nuclei. A difference was seen in the location of efferent terminals between the FL and VP. When the tracer covered the FL, labeled axon terminals were located within the medial and ventrolateral parts of the medial vestibular nucleus, superior vestibular nucleus and y-group. When the tracer covered the VP, labeled axon terminals were located within the caudo-ventral part of posterior interpositus and dentate nuclei, in addition to the medial and ventrolateral parts of the medial vestibular nucleus, superior vestibular nucleus and y-group. Labeled terminals were virtually absent in the basal interstitial nucleus of the cerebellum. On the points of neo- or paleo-cerebellar cortex fiber connections, these results correspond to our previous anatomical observations that the FL received mossy fiber afferents mainly from the vestibular system and nucleus reticularis tegmenti pontis and very little from the pontine nuclei, whereas the VP received mossy afferents mainly from the nucleus reticularis tegmenti pontis and pontine nuclei and very little from the vestibular system. These anatomical observations are consistent with a hypothesis in our previous anatomical and physiological study that the primate FL and VP mediate rather different functional roles in the oculomotor control.

The reticulovestibular projections of the brainstem in the rabbit were studied by the retrograde transport of horseradish peroxidase (HRP). After selective iontophoretic injections of the tracer into various subdivisions of the vestibular nuclear complex (VNC), labeled neurons were found in defined regions of the reticular formation (RF) of the caudal pons and the rostral medulla. The results indicate that all four vestibular nuclei receive projection from RF. This projection is bilateral with a contralateral predominance. The major projection originates from dorsal and dorsolateral regions of the caudal pontine reticular nucleus (RPc) and the gigantocellular reticular nucleus (RGc) at the transitional level between them. A modest projection originates from pars alpha of the caudal pontine reticular nucleus (RPc alpha), the parvocellular reticular nucleus (Rpc) and pars alpha of the parvocellular nucleus (Rpc alpha), mostly from their ventral regions. A small projection arises from pars alpha of the gigantocellular reticular nucleus (RGc alpha), as well as from the ventral reticular subnucleus (Rv) and cell group a in the caudal aspect of the medulla. No clear-cut topical relationship was noted between the location of neurons in RF and projection site in VNC. The superior vestibular nucleus (SV) and the medial vestibular nucleus (MV) receive projections exclusively from RPc and RGc, whereas the lateral reticular nucleus (LV) and the inferior vestibular nucleus (IV) receive additional projections from the remaining RF nuclei. The termination areas of reticular fibers within SV and IV seem to be diffuse but in MV and LV there is a clear preponderance to the regions located ventrally. The present study has established cells of origin for the reticulovestibular projections from the pontomedullary RF to individual VNC nuclei in the rabbit.

Previous studies have demonstrated that the administration of Ginkgo biloba extract (EGb 761) improves the compensation of the vestibular syndrome induced by transection of the VIIIth nerve. To investigate the mechanisms at play, the vestibular nuclei of alert guinea pigs were perfused with EGb 761. This perfusion always induced a stereotyped reversible postural syndrome that was the mirror image of the syndrome provoked by the unilateral lesion of the otolithical receptors. This result supports the hypothesis that EGb 761 has a direct excitatory effect on the lateral vestibular nuclei (LVN) neurons. In a second step, we quantified the horizontal vestibuloocular reflex (HVOR) of the normal guinea pig following IP injection of EGb 761. In normal guinea pig, IP administration of EGb 761 led to a reversible, dose-dependent decrease of the HVOR gain without affecting the phase of the reflex. These data help to explain the therapeutic effects of EGb 761 during vestibular syndromes and strongly suggest an impact at the neuronal level.

The organization of the secondary vestibular projections onto the cerebellar paramedian lobule (PML) and possible reciprocal corticovestibular connections were investigated by the retrograde horseradish (HRP) technique in the rabbit. Following injections of the tracer into the vestibular nuclear complex (VNC), an ill-defined, sagittal band composed of numerous labelled Purkinje cells was found ipsilaterally throughout the length of the lateral portion of the vermis, the ventral paraflocculus and the flocculus. However, no labelled Purkinje cells were found in the cortex of the PML. The results indicate that zone B, considered to give rise to cerebellar corticovestibular projections, is not present in the rabbit PML. After injections of HRP into the PML, the retrograde labelling pattern in the VNC was analyzed, in relation to the climbing fiber zones identified by retrograde labelling in the inferior olive. No clear-cut correspondence could be found between the vestibular subdivisions and climbing fiber zones in the PML, except that only the interstitial nucleus of the vestibular nerve projects into zone D1 in sublobules e and d. There were no vestibular projections to zone D2. The only salient feature was that cells projecting onto zones C2, C1 and C3 of the PML were arranged rostrocaudally in the inferior vestibular nucleus and the caudal portion of the medial vestibular nucleus. In addition, a topical relationship was found between parts of the VNC and sublobules of the PML.

The morphology of single physiologically-identified lateral and medial vestibulospinal tract (LVST and MVST) axons was analysed, using intracellular staining with horseradish peroxidase (HRP) and three-dimensional reconstruction of axonal trajectories in the cat. Axons were penetrated in the cervical cord at C1-C8 with a microelectrode filled with 7% HRP. These axons were identified as vestibulospinal axons by their monosynaptic responses to stimulation of the vestibular nerve and further classified as either LVST or MVST axons by their responses to stimulation of the LVST and MVST. The stained axons could be traced over distances of 3-16 mm rostrocaudally. Within these lengths, both LVST and MVST axons were found to have multiple axon collaterals at different segments in the cervical cord. Up to seven collaterals were given off from the stems of MVST axons and LVST axons. The LVST axons included both neurones terminating at the cervical cord and those projecting further caudally to the thoracic or lumbar cord. Each collateral of these LVST axons, after entering into the gray matter, ramified successively in a delta-like fashion and terminated mainly in lamina VIII and in the medial part of lamina VII. Many boutons of both terminal and en passant types seemed to make contact with the cell bodies and proximal dendrites of neurones in the ventromedial nucleus (VM). Each collateral had a narrow rostrocaudal extension (0.2-1.6 mm, average 0.8 mm) in the gray matter in contrast to a much wider intercollateral interval (average 1.5 mm), so that there were gaps free from terminal boutons between adjacent collateral arborizations. The morphology of axon collaterals of MVST axons was very similar to that of LVST axons. The rostrocaudal extent of single axon collaterals was very restricted (0.3-2.1 mm) in contrast to the wide spread in a mediolateral or a dorsoventral direction. MVST axons had intensive projections to the upper cervical cord with multiple axon collaterals. One to seven collaterals of single MVST axons were found at C1-C3. Terminals of MVST axons were distributed in laminae VII, VIII and IX, including the VM, the nucleus spinalis n. accessorii (SA), and the commissural nucleus. Many terminals seemed to make contact with retrogradely-labelled motoneurones of neck muscles. Both axosomatic and axodendritic contacts were observed on motoneurones in various sizes. Some collaterals gave rise to terminal arborizations in both the VM and the SA. These results suggest that single LVST and MVST axons may control excitability of multiple dorsal axial muscles concurrently with their multiple axon collaterals at multisegmental levels.

Experiments were performed to study the projection of the group y of the vestibular nuclei and the dentate and fastigial nuclei of the cerebellum to the interstitial nucleus of Cajal (INC) in cats by using retrograde axonal transport of horseradish peroxidase (HRP) and electrophysiological methods; and to study the vestibular responses of such projection neurons. Following injections of HRP into the unilateral INC, with partial involvement of the surrounding reticular formation, including the nucleus of Darkschewitsch (ND), many retrogradely labeled neurons were found in the dorsal part of the group y nucleus contralateral to the injection site. Labeled cells were also seen in the contralateral dentate nucleus, frequently in its caudal-ventral part, and in the contralateral fastigial nucleus at all rostrocaudal levels, but most frequently in its caudal part. In electrophysiological experiments performed on cats anesthetized with alpha-chloralose or N2O and paralyzed with gallamine, group y, dentate and fastigial nuclei neurons were antidromically activated by weak stimuli that were confined to the contralateral INC. Depth-threshold curves for antidromic activation of such neurons revealed that the lowest threshold points were within the INC, but not in the ND. The INC-projecting neurons in the group y and dentate nuclei did not respond to electrical stimulation of the ipsilateral or contralateral vestibular nerve, indicating that they do not receive direct labyrinthine inputs. On the contrary, many fastigial neurons projecting to the INC responded to labyrinthine stimulation, suggesting that they may be involved in the vestibular reflexes. These results suggest a difference in properties of INC-projecting neurons in these nuclei.

A synopsis of physiological and anatomical results is presented that leads to the conclusion that experimental data have to be interpreted in a context meaningful for the system investigated. For example, since there is an obvious spatial relationship between semicircular canals and extraocular muscles, the interdependence between the three-neurone-arc circuitry, and vestibular and visual signals follows quite naturally from a common geometry inherent in the sensory and motor periphery. It is emphasized that signals related to compensatory eye movements have to be interpreted within a vestibular/eye muscle frame of reference. By the same argument, when dealing with the head-neck movement system, the appropriate reference frame will have to be applied to arrive at a meaningful interpretation of related sensorimotor functions. Thus, in general terms, each system has to be interpreted within its own meaningful biological context.