Long descending motor tract axons and their control of neck and axial muscles

Progress in Brain Research, Vol. 151 ISSN 0079-6123 Copyright r 2006 Elsevier B.V. All rights reserved

CHAPTER 17

Long descending motor tract axons and their control of neck and axial muscles Yoshikazu Shinoda, Yuriko Sugiuchi, Yoshiko Izawa and Yuko Hata Department of Systems Neurophysiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan

Abstract: 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. movements, since lesions of the pyramidal system produced impairment of voluntary movements such as paralysis of limb muscles, decreased or increased stretch reflex, and appearance of abnormal reflex (Babinski sign). On the other hand, the other long descending motor tract systems other than the pyramidal tract including the cerebellum and the basal ganglia were called the extrapyramidal system, and this system was considered to be mainly involved in control of posture rather than limb movements. This dichotomy between the pyramidal tract system and the extrapyramidal system has not been tenable any more, since movements of limbs are still possible after the sectioning of the bilateral pyramids (Lawrence and Kuypers, 1968a, b). Figure 1A summarizes the present view of the long descending motor tract systems. After the sectioning of the pyramidal tract, long descending tracts that receive inputs from the cerebral cortex still exist in the brainstem

Introduction Classical and current view of long descending motor tract systems The motor cortex is considered to be a higher center for voluntary movements. Corticofugal neurons from the motor cortex to the spinal cord pass through the medullary pyramid, so that this pathway is called the pyramidal tract. It was generally believed that the output from the motor cortex was conveyed only through the pyramidal tract to the spinal cord. Therefore, this system has been called the pyramidal tract system, and this pathway was considered to be the only pathway that mediates control signals for voluntary Corresponding author. Tel.: +81 3 58035 5155; Fax: +81 3 5803 5155; E-mail: [email protected] DOI: 10.1016/S0079-6123(05)51017-3

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528 Fig. 1. (A) Functional classification of long descending motor tract systems originating from the cerebral cortex and the brainstem and projecting to the spinal cord. (B) Cytoarchitectonic classification of the spinal gray matter (laminae I–IX of Rexed) and the distribution of spinal motoneurons (left) and interneurons (right). Laminae I–IV for sensory transmission, laminae V–VIII (the intermediate zone) for motor integration, and lamina IX for the motor nuclei (see the details in the text). In the ventral horn, the motor nuclei for distal muscles are located more laterally, whereas the motor nuclei for proximal muscle are located more medially in lamina IX. Interneuron groups (a–d) in different portions of the intermediate zone project to the motor nuclei of different groups of muscles in a specific topographic manner. Laterally located interneurons (a) tend to project to distal limb muscle motoneurons and more medially located interneuron groups, b–d, mainly project to proximal, girdle and axial muscles, respectively. Interneuron group d also contains commissural neurons that project via the anterior commissure to contralateral axial motoneurons (modified from Kuypers, 1973).

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and they convey signals for voluntary movements of limbs to the spinal cord. Among them, there are two pathways; one that receives input via collaterals of pyramidal tract neurons and the other that receives input from corticofugal neurons of the cerebral cortex other than pyramidal tract neurons. The former is called the parapyramidal tract system, which includes the cortico-rubrospinal and cortico-reticulospinal connections, and the latter is called cortically originating extrapyramidal system. Except these long descending motor tract systems that are related to the cerebral cortex, the long descending motor tract system that does not receive cerebral input exists and is called the extrapyramidal system in a narrow sense. Readers interested in the changing views of the motor cortex and the pyramidal tract should consult excellent monographs by Phillips and Porter (1977) and Porter and Lemon (1995).

General organization of the motor nuclei in the spinal cord The final targets of these long descending motor tracts, either directly or indirectly, are motoneurons of muscles in different parts of the body. Somatic motoneurons which extend their axons through the ventral root to a given axial or limb muscle are arranged in a longitudinal, column-like fashion in the ventral horn (Romanes, 1951; Sprague, 1951; Burke et al., 1977). The longitudinal columns innervating individual muscles are grouped into the medial and lateral longitudinal aggregates. The medial aggregate is made up of motoneuronal columns of vertebral muscles innervated by the dorsal and the ventral rami of the ventral root and exists throughout the spinal cord, whereas the lateral aggregate of motoneuronal columns for other appendicular (limb) muscles innervated by the ventral rami exists only in the cervical and the lumbar enlargements due to the additional longitudinal columns for the muscles intrinsic to the extremities, and fuses to the medial aggregate in the upper cervical and the upper thoracic cord, and the lower thoracic cord. Figure 1B (left) summarizes the general arrangement of the motor nuclei in the spinal ventral horn

(lamina IX of Rexed) for muscles in different parts of the body. In general, the motor nuclei for distal muscles are located more laterally and those for proximal muscles are located more medially in the ventral horn. More specifically, the motor nuclei for axial muscles are located most medially, those for limb muscles (appendicular muscles) are most laterally, and those for girdle muscles are located between the above two. Among the limb muscles, extensors are located more medially than flexors, so that limb flexors, especially intrinsic muscles, are located in the most lateral part of the ventral horn where corticospinal axons most extensively terminate directly on motoneurons in both monkeys and humans (Lawrence and Kuypers, 1968a).

General organization of interneurons in the spinal cord As motoneurons innervating axial and limb muscles are located in different areas of the ventral horn (musculotopic organization), interneurons terminating upon motoneurons of these two groups of muscles are also arranged in different portions of the spinal intermediate zone (laminae V–VIII) (Rexed, 1954; Kuypers, 1981). The spinal gray matter is divided into subdivisions dorsoventrally from lamina I to lamina X, based on the cytoarchitecture (Fig. 1B, left) (Rexed, 1954). Laminae I–IV belong to the dorsal horn, which is mainly related to sensory relays. The most ventral part, lamina IX, belongs to the ventral horn, which only includes motoneurons. Laminae V–VIII, which are located between the dorsal and ventral horns, are called the intermediate zone. This intermediate zone is responsible for motor integration, since it receives inputs from the spinal afferents such as Groups Ia and Ib and also inputs from the long descending motor tract systems, and send its outputs to motoneurons. Spinal interneurons have been classified into segmental and propriospinal interneurons. Interneurons that project only to the same segment are called segmental interneurons, whereas interneurons that project to the other segments are called propriospinal interneurons. However, recent intracellular staining revealed that most ‘‘segmental’’

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interneurons extend their axons once outside the gray matter into the white matter, and again enter the gray matter at different segments. Therefore, this dichotomous division of the spinal interneurons is no longer clear. Interneurons in the intermediate zone may be divided into two groups; interneurons located in the medioventral part of the intermediate zone (lamina VIII and its adjacent lamina VII) and interneurons in the dorsal and lateral parts of the intermediate zone (laminae V–VII). These interneurons in different parts of the intermediate zone (different interneuron groups a–d in Fig. 1B, right) distribute their fibers to specific parts of the lateral and ventral funiculi in the white matter and terminate on specific motoneuronal groups in the ventral horn (see the details in the legend of Fig. 1B).

Classification of long descending motor systems When considering the functions of the long descending motor tract pathways, it should be realized that their functions are not only determined by (1) inputs to cells of their origin, but also by (2) their terminations on target cells in the spinal cord. Various long descending motor tracts of supraspinal origin are known to terminate in different areas of the spinal gray matter (Brodal, 1981; Holstege, 1988), so that they influence differentially motoneurons of different groups of muscles and interneurons innervating them. The brainstem pathways terminating in the spinal intermediate zone as well as the motoneuronal cell groups probably subserve mainly motor functions. The subcorticospinal pathways, i.e., pathways from the subcortical structures to the spinal cord (Fig. 1A), have been grouped into the medial and lateral systems based upon the location of such pathways in the spinal white matter and their terminal distribution in the spinal cord (Kuypers et al., 1962). The medial system terminates in the ventromedial part of the intermediate zone, whereas the lateral system terminates in the dorsal and lateral parts of the intermediate zone of the spinal gray matter. Extending this classification to the entire long descending motor tract systems including both the corticospinal and subcorticospinal

system, the long descending motor tract system is subdivided into two major systems (see Fig. 5A), although the terminal distribution of corticospinal tract (CST) fibers overlaps that of either of the two subcorticospinal systems: (1) the medial system originates in the brainstem (the medial subcorticospinal system), runs in the ventral funiculus, and terminates in the mediodorsal part of the ventral horn and its adjacent part of the intermediate zone; and (2) the lateral system consists of the corticospinal system and the lateral subcorticospinal system, runs in the dorsal lateral funiculus, and terminates in the lateral and dorsal parts of the intermediate zone (Kuypers, 1964). The lateral system consists of the CST and the rubrospinal tract (RBST), whereas the medial system consists of the reticulospinal tract (RST), the vestibulospinal tract (VST), the tectospinal tract (TST), and the interstitiospinal tract (IST). For spinal termination fields of different long descending motor tracts, see Holstege (1988).

New aspects of long descending motor tract axons It has been tacitly assumed that the pyramidal tract, which is the main output pathway from the motor cortex to the spinal cord for conveying control signals of voluntary movement, consists of private lines connecting a point in the motor cortex to a single muscle, as a motoneuron innervates a single muscle. Accordingly, CST neurons, often called as pyramidal tract neurons, have been referred to as upper motoneurons, and spinal and brainstem motoneurons as lower motoneurons. Other long descending motor tracts also have been considered to be similar to the pyramidal tract in this aspect. However, the above notion of a long descending motor tract referred to as a private line is no longer tenable, since recent studies showed that axons of all major long descending motor tracts send axon collaterals to multiple spinal segments. This situation was first described by Abzug et al. (1974), who found that 50% of lateral vestibulospinal tract (LVST) neurons, which sent axon branches to C6-Tl segments, were also antidromically driven by stimulation of the lumbar spinal cord. A similar percentage of RST neurons sent

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branches to the cervical gray matter as well as to the first lumbar segment (Peterson et al., 1975). More surprisingly, 6% of CST neurons activated from the cervical gray matter (C4–C8) projected to the first lumbar segment and 24% of CST neurons activated from the cervical gray matter projected to the thoracic cord (Shinoda et al., 1976). Similarly, 45% and 5% of RBST neurons projecting to the cervical gray matter sent axon branches to the thoracic cord and below, and to the first lumbar level, respectively (Shinoda et al., 1977). Furthermore, it turned out that virtually all CST neurons examined in the forelimb area of the motor cortex had three to seven axon collaterals at widely separated segments of the cervical and the higher thoracic cord (Shinoda et al., 1976, 1986b). In addition, multiple axon collaterals of RBST neurons were also demonstrated at different spinal segments (Shinoda et al., 1977). These results have indicated that single motor tract axons are not a simple private line connecting the cells of origin and motoneurons for a single muscle, but instead they may exert simultaneous influences on different groups of spinal interneurons and motoneurons of multiple muscles at widely separated spinal segments. In fact, single corticospinal axons terminated on motoneurons of multiple muscles in the monkey (Shinoda et al., 1981).

The purpose of this chapter is to briefly review the basic organizations of axial and neck muscles and their motor nuclei, and the general characteristics of the lateral and medial long descending motor tract systems, and to finally describe the intraspinal trajectories of single long descending motor tract axons in the medial descending motor tract system controlling head movements. Readers interested in the classical anatomy of descending motor pathways should consult excellent reviews by Kuypers (1981) and Holstege (1988). Basic organization of axial muscles in the neck and back General arrangements of the epaxial musculature In comparative anatomy of the somatic musculature system, axial muscles are divided by the horizontal (longitudinal) myoseptum into dorsal and ventral muscle groups. Muscles dorsal to the horizontal septum and innervated by the dorsal rami of the ventral root are called epaxial muscles (Mm. dorsi proprii, Mm. tranci dorsales), whereas those ventral to it and innervated by the ventral rami of the ventral root are called hypaxial muscles (Mm. tranci ventrales) (Fig. 2). Based on the investigation of phylogenetic transformations of

Fig. 2. Classification of the epaxial musculature and its spinal innervation pattern (slightly modified from Nishi, 1916). The nomenclature of D0 (L) and D1–D3 is based on the observation that the prototype of these muscle groups in vertebrates is found in the tail musculature of the shark (see Fig. 1Fa in Sugiuchi and Shinoda, 1992).

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the epaxial muscles, they may be further divided into two longitudinal columns, lateral and medial (lateraler und medialer La¨ngszug, as described by Gegenbauer, 1896); correspondingly, the spinal dorsal rami are divided into lateral and medial branches. In the cervical region the medial longitudinal column is more developed, and in the lumbar region the lateral longitudinal column is more developed. The lateral longitudinal column is composed of the iliocostalis group (D0 or L; muscles lying between the proximal ribs) and the longissimus group (D1; muscles extending between the transverse processes and the articular processes of the vertebrae) (Fig. 2). The medial longitudinal column, which is also called the transversospinalis group (muscles extending between the transverse processes and the spinous processes of the vertebrae), consists of the interspinalis, rotatores, multifidus, spinalis, and semispinalis muscles. Nishi (1916, 1963) further divided the transversospinalis into the semispinalis and the multifidus groups. The semispinalis group (D2) consists of the spinalis and semispinalis, and the multifidus group (D3) consists of the interspinalis, rotatores, and multifidus. The transversospinales are innervated by the medial branches of the dorsal rami, and the longissimus and the iliocostales are innervated by the lateral branches of the dorsal rami (Fig. 2). Within the epaxial muscle system, the longer muscles run superficial to the deeper short muscles. According to Vallois (1922), Nishi (1938), and later Slijper (1946), the longer muscles are phylogenetically more recent.

Organization of the motor nuclei innervating thoracic epaxial muscles Sprague (1948, 1951) reported that the cells of the dorsal rami are separated sharply from those of the ventral rami in the ventral horn of the segments innervating the limbs, but that the cells of both the dorsal and ventral rami are widespread and extensively overlapped in the ventral horn of the thoracic cord. Since then, the distribution of the motor nuclei for individual epaxial muscles had not been investigated for a long time. Brink et al. (1979) and Smith and Hollyday (1983), using horseradish peroxidase (HRP) as a retrograde

tracer, determined the motor nuclei for some of the trunk muscles in the rat. Later, we made a systematic investigation of the location of the motor nuclei for all epaxial muscles in the thoracic region of the cat (Sugiuchi and Shinoda, 1992). HRP or fluorescent dyes (Fluoro-Gold, fast blue, propidium iodide, and diamino yellow) were applied to the cut ends of individual motor nerves innervating thoracic epaxial muscles of the first to the eighth thoracic segments. The results were almost identical throughout all spinal segments investigated; therefore, the localization of the motor nuclei at the fifth thoracic segment (T5) will be shown as a representative example (Fig. 3A). Motoneurons for epaxial muscles were found in the ventromedial portion of the ventral horn, whereas those for hypaxial muscles were found in the ventrolateral and the central portions of the ventral horn. This finding is in good agreement with the results in the rat by Smith and Hollyday (1983). Motoneurons for a particular epaxial muscle are distributed in a longitudinal column in the characteristic position of the ventral horn as observed for limb muscles (Burke et al., 1977). Within the motor nuclei for the epaxial muscles the motor nuclei for the multifidus group (D3), the semispinalis group (D2), the longissimus group (D1), and the iliocostalis group (D0) are located in that order from the medial to the lateral portion of the ventral horn (Fig. 3A). Among the multifidus group, the motor nucleus for the rotatores is located more dorsomedially than that for the multifidus. This organization of the motor nuclei is closely related to the organization of the muscles they innervate: the mediolateral arrangement of individual thoracic epaxial muscles is represented by the mediolateral localization of their corresponding motor nuclei in the ventral horn (compare Figs. 2 and 3A). Longitudinal columns for different muscles were considered to overlap extensively (Sprague, 1951; Smith and Hollyday, 1983). To examine the interrelationship between different motor nuclei, we used a multiple labeling method with fluorescent retrograde tracers. With this method, motoneurons of two to four different motor nuclei could be labeled with different fluorescent dyes in the same section of the ventral horn. In each transverse section, motoneurons of one motor nucleus were segregated

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Fig. 3. Organization of the motor nuclei at T5 and C3. (A) Topographic organization of the motor nuclei at T5 innervating thoracic epaxial muscles. HRP was injected into individual muscle nerves at T5 and labeled motoneurons were plotted on each representative section (200 mm thick). The summary diagram on the lower right indicates the locations of the motor nuclei for thoracic epaxial muscles. (B) Topographic organization of the motor nuclei at C3 innervating neck muscles. (Upper left) Motoneurons labeled after injection of HRP into the ventral root at C3 (left) and the spinal accessory nerve (right) are plotted on a representative transverse section (200 mm thick). (Lower left and upper right) Two motor nuclei are labeled, one on each side of the spinal cord. (Lower right) Summary diagram of the motor nuclei for neck muscles at C3 (from Sugiuchi and Shinoda, 1992).

from those of another motor nucleus. In other words, motoneurons of adjacent motor nuclei are interdigitated rather than intermingled, although there is a slight overlap at the border area.

Organization of neck muscles and their motor nuclei Neck epaxial muscles are divided into four groups as back epaxial muscles (Fig. 2). In the cat, the

complexus and the biventer cervicis, which belong to the semispinalis group (D2), are the largest muscles. The rectus capitis dorsalis and the obliquus capitis caudalis, which belong to the multifidus group (D3), are rather massive and important for neck movements at atlanto-axial joints. The longissimus group (D1), which is composed of the longissimus capitis, the obliquus capitis cranialis, and the splenius, is located lateral to the semispinalis group. The detailed description

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of the gross anatomy of neck muscles is provided in the comprehensive review by Richmond and Vidal (1988). The location of the motor nuclei for some of the large neck muscles has been studied in the cat by Richmond et al. (1978), using HRP. Their results indicated that motor nuclei for large neck muscles such as the splenius, biventer, and complexus occupied a wide area in the ventral horn and they overlapped each other extensively. We systematically investigated the location of the motor nuclei for neck muscles including other small neck muscles in the cat using the multiple labeling method. Our study confirmed some of the findings of Richmond et al. (1978) and added some evidence of the location of the motor nuclei for other small neck muscles (Sugiuchi and Shinoda, 1992). The results are briefly summarized in Fig. 3B. Motoneurons sending their axons in the ventral radices (roots) are located in the central and ventromedial portions of the ventral horn, whereas motoneurons of the nucleus spinalis n. accessorii (SA) innervating the sternomastoid and cleidomastoid muscles are located more dorsolaterally along the ventrolateral border of the ventral horn (upper left diagram of Fig. 3B). Motoneurons for individual dorsal neck muscles occupy characteristic positions in the transverse plane of the ventral horn, and the overlapping between adjacent motor nuclei is rather small. At C3, the motor nucleus for the semispinalis is located in the ventral tip, that for the splenius more dorsolaterally, and that for the longissimus more dorsomedially (lower right diagram of Fig. 3B). At C2, the motor nucleus for the obliquus capitis caudalis appears more ventrally than that for the semispinalis. At C1, the motor nucleus for the rectus capitis dorsalis appears more dorsally than that for the obliquus capitis caudalis. Since the neck muscles are highly specialized in higher vertebrates, it is not easy to find their counterparts in the thoracic axial musculature in which the most basic pattern of the arrangement of the axial musculature remains, and further systematic analysis will be required to identify the homologous counterparts of individual neck muscles in relation to their counterparts in the thoracic and lumbar regions.

Lateral vs. medial long descending motor tract systems As mentioned in the ‘‘Introduction,’’ long descending motor tracts of supraspinal origin are classified into the lateral and medial descending groups based on anatomical and behavioral observations after lesions of these two long descending motor tract groups (Lawrence and Kuypers, 1968a, b), although they are not completely separated. The general characteristics of these two descending systems are briefly summarized below (see a diagram in Fig. 5 for the summary of this section) (Kuypers, 1981). The lateral descending motor tract group This group is mainly composed of the CST and RBST, which run in the dorsal part of the lateral funiculus of the spinal cord. The CST originates from the sensorimotor cortex (mainly the motor cortex) and terminates in laminae I–VII in the lower mammals, in addition, in lamina VIII in higher mammals, and in lamina IX in the primates. In the primates, the bank area of the precentral motor cortex innervates directly the motor nuclei of distal limb muscles, and the CST arising from the anterior portion of the motor cortex (body and limb girdle areas) and the premotor area bilaterally terminates at medial laminae VII–VIII. The RBST originating from the magnocellular portion of the red nucleus, after crossing the midline, runs in the ventrolateral part of the medulla and terminates in laminae V–VII in cats and also in lamina IX in primates. With the ascent of the phylogeny, the parvocellular portion of the red nucleus dominates, and the RBST from the magnocellular portion becomes fractional, and almost negligible in the humans. The common features of the CST and RBST are roughly summarized as follows (see Fig. 5A, right and 5B) (Phillips and Porter, 1977; Porter and Lemon, 1995). 1. Both the CST and the RBST mainly run in the contralateral lateral funiculus of the spinal cord (Fig. 4). 2. Both the CST and the RBST mainly control distal limb muscles rather than axial and proximal muscles.

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Fig. 4. Schematic representation of the spinal white matter location of the various descending pathways, specifically involved in control of neck and axial muscle inter- and motoneurons. On the left a drawing is made of the C2 spinal segment and on the right a drawing of the T12 spinal segment. It must be emphasized that this scheme does not give any indication about the number of fibers belonging to the different descending pathway. It must also be noted that many of the descending fiber systems pass through the same areas as indicated in the drawing (e.g., propriospinal, reticulospinal, and corticospinal fibers). PAG, periaqueductal gray (from Holstege, 1988).

3. They exert stronger excitatory effects on flexor muscles and stronger inhibitory effects on extensor muscles. 4. In these two systems, excitatory inputs are mediated disynaptically and inhibitory inputs trisynaptically at the shortest to motoneurons in the cat, but in primates, they are mediated mono- and disynaptically, respectively. 5. The motor cortex and the red nucleus receive inputs from the interpositus and the dentate nuclei in the cerebellum. CST neurons receive convergent inputs from the interpositus and dentate nuclei (Shinoda et al., 1992a) and RBST neurons receive input from the interpositus nucleus (Tsukahara et al., 1967).

6. The CST and RBST innervate interneurons spreading in the lateral parts of laminae V–VI to lamina VII. The medial descending motor tract group This group consists of the VST, RST, TST, IST, and fastigiospinal tract. These tracts mainly run in the ventral or medial portions of the brainstem and the ventral funiculus of the spinal cord (Fig. 4), and then exert their effects bilaterally in most cases. These tracts terminate on interneurons spreading from lamina VIII to lamina VII that include long propriospinal neurons and commissural neurons and also on motoneurons innervating axial and proximal limb muscles (see Fig. 5A,

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Fig. 5. (A) Classification of long descending motor tract systems into lateral and medial systems. The lateral system consists of the long descending motor tracts that run in the dorsal part of the lateral funiculus and terminate in the central and the lateral portions of the intermediate zone (laminae V–VII) of the spinal cord. In contrast, the medial system cnsists of the long descending motor tracts that run in the ventral funiculus and terminate in the medial portion of the intermediated zone (lamina VIII and its adjacent lamina VII). (B) Schematic diagram showing the strength of synaptic connections from three different descending motor tract systems onto motoneurons of muscles in different parts of the body. BS, brain stem; CST, corticospinal tract (modified based on Kuypers, 1973).

left and 5B) (Holstege and Kuypers, 1982). The common features of the VST, RST, TST, and IST are roughly summarized below. 1. The medial system is phylogenetically and ontogenetically older than the lateral system. 2. The tracts in the medial system mainly run in the ventral funiculus (Fig. 4). 3. The medial system characteristically steers body, and integrates limb and body movements as well as movement synergisms of individual limbs involving various parts. The lesion of the medial system usually produces motor disturbance of the axial and the proximal muscles including the neck and eyes, without affecting distal limb muscles. 4. The VST contains the LVST that originates from the lateral and descending vestibular nuclei (LVN and DVN, respectively), and the medial VST (MVST) that originates from the medial vestibular nuclei (MVN) and DVN (Brodal et al., 1962). The LVST, mainly receiving otolith input and anterior lobe cerebellar influences, descends ipsilaterally as far as the lumbar spinal cord and exerts excitatory effects on extensor motoneurons and inhibitory effects on flexor motoneurons via Ia inhibitory interneurons in postural control

and body equilibrium (Grillner and Hongo, 1972) (see Fig. 15). The MVST, receiving mainly semicircular canal inputs, descends bilaterally through the medial longitudinal fasciculus (MLF) and exerts monosynaptic excitatory and inhibitory effects on neck and back muscle motoneurons in the vestibulocollic reflex (Wilson and Melvill-Jones, 1979) (see Figs. 15 and 20). 5. The RST is composed of the pontine RST that originates from the pontine reticular formation, descends in the ventral funiculus ipsilaterally, and terminates in medial 1aminae VII and VIII, and of the medullary RST that originates from the medulla, descends bilaterally in the ventrolateral funiculus and terminates mainly in lamina VII (partly in laminae VIII and IX). Some RST neurons receive input from the vestibular organ. Formerly, the facilitatory and inhibitory systems in the reticular formation proposed by Magoun (Magoun and Rhines, 1946; Rhines and Magoun, 1946) were considered to control general muscle tonus of the whole body simultaneously for postural adjustment. But later studies indicated that some groups of RST neurons might control excitability of specific groups of muscles rather than general muscle tone, suggesting that the

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RST might be involved in control of limb movements in addition to postural adjustment (Peterson, 1979). 6. Both VST and RST neurons receive strong input from the fastigial nucleus, which receives vestibular and somatosensory inputs via the cerebellar vermis. A lesion in the fastigial nucleus or the cerebellar vermis is known to produce severe truncal ataxia (Ito, 1984). 7. The TST originates from the superior colliculus and crosses the midline just below the superior colliculus. It passes through the predosal bundle and descends in the ventral portion of the contralateral MLF to the spinal cord (Verhaart, 1964). The IST originates from neurons in the nucleus of Cajal and its vicinity, descends in the dorsal portion of the ipsilateral MLF in the brainstem (Verhaart, 1964), and projects bilaterally to the medial part of the upper cervical ventral horn, via the dorsal part of the ventral funiculus (Holstege and Cowie, 1989). TST and IST neurons receiving visual inputs play an important role in eye and head coordination in orienting responses and do not project below the lower cervical cord (Fukushima, 1987; Grantyn and Berthoz, 1988) (see Fig. 19). Morphologies of single neurons in the medial long descending motor tract system As summarized above in a generalized form, long descending motor tracts, their target motor nuclei and interneurons may be principally segregated into the medial and lateral motor systems. Degeneration staining methods such as the Nauta method combined with lesion experiments were used for identifying the location of descending tracts in the brainstem and spinal cord and their terminal distribution in the spinal cord (Brodal et al., 1962; Verhaart, 1964). More recently, the autoradiographic method and retrograde staining with the enzyme, HRP, made it possible to determine more accurately the location of the tracts and the distribution of cells of their origins. However, it was not possible until the mid-1970s to trace long axons of single neurons from their cell bodies to terminals by using anatomical techniques. Until that time, the Golgi staining

method was the only method with which the morphology of single neurons could be traced. However, even with this preparation, we could trace only neuronal structures that could be observed within a single section of 100 mm thickness. For visualization of the entire axonal morphology of a single neuron, especially one with a relatively long axon, new methods had to be developed, particularly ones which would bring into view the entire morphology of single, functionally identified neurons in the central nervous system (CNS). HRP was shown to be particularly valuable for intracellular staining of single physiologically identified neurons (Jankowska et al., 1976; Kitai et al., 1976; Snow et al., 1976). Admittedly, all of the processes of a single neuron labeled with HRP may not be visualized in a single section. Reconstruction of the axonal trajectory using serial sections, however, can reveal the entire axonal trajectory of a single-labeled neuron for a distance of 10–30 mm in the mammalian CNS (for review, see Shinoda, 1999). By using intracellular staining with HRP, Shinoda and his colleagues first visualized intraspinal axonal morphologies of single neurons in the lateral long descending motor tracts such as CST neurons (Shinoda et al., 1976, 1981, 1986a, b; Futami et al., 1979) and RBST neurons (Shinoda et al., 1977, 1982). These studies revealed that single CST and RBST axons have multiple axon collaterals at multiple spinal segments and may control excitability of multiple muscles simultaneously. Later, Shinoda’s group further visualized the intraspinal morphologies of single medial long descending motor tract axons such as VST, TST, and RST neurons. In this section, we will summarize the morphological features of single neurons in the medial motor tract system which plays an important role for head and axial movements.

The vestibulospinal tract Among the medial long descending motor tracts, the vestibulospinal system has been most extensively examined both anatomically and electrophysiologically (for physiology of the vestibular system, see an excellent monograph by Wilson and Melvill-Jones, 1979). The VST is composed of the

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LVST and the MVST (Figs. 4 and 15A) (Brodal et al., 1962; Wilson and Melvill-Jones, 1979; Holstege, 1988). Previous studies using a degeneration method showed that the MVST arose only from the MVN and descended bilaterally in the MLF (Nyberg-Hansen, 1964), and the LVST arose only from the LVN and descended only ipsilaterally to the lumbar spinal cord (Pompeiano and Brodal, 1957; Nyberg-Hansen and Mascitti, 1964). However, the information about the exact locations of neurons of origin of the LVST and the MVST had not been available until new anatomical tracer studies were introduced. To determine the distribution of cells of origin of the VSTs, we injected HRP into the MLF in the brainstem or the spinal cord in combination with a section experiment, and retrogradely labeled cells were mapped in the vestibular nuclei in the cat.

Distribution of MVST neurons in the vestibular nuclei (1) Injection of HRP into the unilateral MLF at the level of the caudal end of the inferior olive (injection site shown in the inset of Fig. 6). Fig. 6 shows the distribution of retrogradely labeled cells in the vestibular nuclei after HRP injection into the unilateral MLF. The injection site mainly covered the MLF on one side, but might slightly spread to the contralateral MLF. Labeled cells were distributed bilaterally in the area where the MVN, the LVN and the DVN meet, and continuously in the further caudal area where the MVN and the DVN meet. Dorsal view of the distribution of the same labeled cells (Fig. 8A) shows that there are two groups of labeled cells; the rostral group is located in the area where the three nuclei meet and the caudal group in the

Fig. 6. Distribution of medial vestibulospinal tract (MVST) neurons labeled after injection of HRP into the paramedian region including the unilateral medial longitudinal fasciculus (MLF) at the level of the caudal end of the inferior olive. Labeled neurons in five serial coronal sections of 100 mm thickness are plotted in representative sections shown at 500 mm intervals. Shaded and hatched areas in the top inset diagram in this and Fig. 8A show the injection site of HRP. One dot indicates one labeled neuron. Thin lines indicate labeled fibers. The same arrangement for displaying labeled neurons will be used in Figs. 6, 7, and 9. Shaded areas in sections 15 and 16 indicate injection site. S, superior vestibular nucleus; M, medial vestibular nucleus; L, lateral vestibular nucleus; D, descending vestibular nucleus; VII, facial nerve; VIII, vestibular nerve.

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caudal one-third of the MVN and the caudal half of the DVN. The labeled cells in the caudal group were smaller than those in the rostral group. (2) Injection of HRP into the first cervical spinal cord on one side with the hemisection of the medulla on the same side except the MLF (injection site at C1 and section in the medulla shown in the inset of Fig. 7). The distribution pattern of retrogradely labeled cells was very similar to that in the MLF injection (Fig. 6 and compare Fig. 8A and B). Labeled cells were found bilaterally around the area where the rostral two-thirds of the MVN, the rostral half of the DVN and the caudal part of the LVN meet, and around the area where the caudal one-third of the MVN and the caudal half of the DVN meet (Fig. 8B). This result complements the results in Fig. 6. Distribution of LVST neurons in the vestibular nuclei (1) Injection of HRP into the first cervical spinal cord on one side with the section of the medulla

covering the bilateral MLF (injection site shown in the inset of Fig. 9). To determine the distribution of LVST neurons in the vestibular nuclei, HRP was injected into the one half of the first cervical cord and a transverse section was made in the medulla covering the bilateral MLFs. Labeled cells were abundantly distributed in the ipsilateral LVN and its adjacent DVN (Fig. 9). The other small group of labeled cells was found in the bilateral caudal MVN and DVN (Fig. 8C). (2) Injection of HRP into the one half of the fourth lumbar spinal cord with the bilateral MLFs sectioned at the medulla (Fig. 8D). Labeled cells were mainly found in the ipsilateral LVN, and a very small number of cells were found in the bilateral caudal MVN and DVN. The number of the labeled cells was much smaller than that of the cells labeled after the cervical injection (Fig. 8C). The above findings have shown that the MVST arises from two groups of vestibular nucleus

Fig. 7. Distribution of MVST neurons labeled by injection of HRP into the left half of the first cervical cord after making a large transverse section in the left half of the brainstem, except the MLF. Injection site in the cervical cord covered the entire ventral funiculus, most of the dorsal funiculus, ventral part of the lateral funiculus, and most of the gray matter. Hatched and shaded areas in the upper left inset diagrams show the injection site in the cervical cord and the lesion in the brainstem, respectively. The same arrangement for displaying the injection site and lesion will be used in Figs. 8B–D and 9.

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Fig. 8. Dorsal view of the distribution of labeled neurons in the vestibular nuclei. (A) Labeled neurons in the vestibular nuclei shown in Fig. 6 after injection of HRP into the paramedian region including the unilateral MLF at the level of the caudal end of the inferior olive. (B) Vestibular nuclei neurons labeled by injection of HRP into the left half of the first cervical cord after making a large transverse section in the left half of the brain stem except the MLF (the same material shown in Fig. 7). (C) Labeled neurons in the vestibular nuclei shown in Fig. 9. Injection of HRP was made into the left half of the first cervical cord after making a large transverse section of the paramedian region in the brainstem including the bilateral MLFs. (D) Neurons in the vestibular nuclei labeled by injection of HRP into the left half of the fourth lumber cord after making a transverse section of the bilateral MLFs. Filled circles and triangles indicate neurons in the lateral (LVN) and medial vestibular nucleus (MVN), respectively. Open circles and triangles indicate those in the descending (DVN) and superior vestibular nucleus (SVN), respectively. G, facial genu.

neurons, the main rostral group that is located in the rostral MVN, caudal LVN, and rostral DVN, and the caudal group that is located in the caudal MVN and DVN. This caudal group corresponds to neurons of origin of the caudal VST reported by Peterson and Coulter (1977) and Peterson et al. (1978). Our data have also shown that the LVST originates mainly from the LVN but also from the rostral DVN on the ipsilateral side. In addition, cells that were labeled by injecting HRP into the unilateral half of the cervical or lumbar spinal cord with the section of the bilateral MLFs were distributed in the caudal DVN and MVN.

In brief, as summarized in Fig. 8, the MVST originates from the bilateral vestibular nuclei, most extensively from the area where the MVN, the LVN and the DVN meet, whereas the LVST originates mainly from the ipsilateral LVN and its adjacent DVN. In addition, both the MVST and the LVST arise less extensively from the bilateral caudal DVN and MVN. Projection areas of primary vestibular afferents in the vestibular nuclei The distribution of axon terminals of primary vestibular afferents were examined, using the

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Fig. 9. Distribution of LVST neurons labeled by injection of HRP into the left half of the first cervical cord after making a large transverse section of the paramedian region in the brain stem including the bilateral MLFs.

degeneration method, the autoradiographic or the HRP method. Lorente de No´ (1933) revealed (a) that fibers originating from the utriculus and the anterior and horizontal semicircular canals are located in the superior vestibular ganglion, and (b) that fibers from the sacculus and the posterior canal are in the inferior ganglion. By utilizing these topographical characteristics, attempts were made to correlate the terminal distribution in the vestibular nuclei with the vestibular nerves from the different endorgans by selective lesions (Walberg et al., 1958; Stein and Carpenter, 1967; Gacek, 1969, Korte, 1979) or injecting markers (Carlton and Carpenter, 1984) to a limited portion of ganglions. Both afferents arising from the semicircular canals and otolith organs project to overlapping areas in the vestibular nuclei, although they project to specific areas. More recently, primary vestibular afferents were stained with intracellular injection of HRP after identification of their electrophysiological properties, and the axonal trajectories of single semicircular canal nerves (Ishizuka

et al., 1982; Mannen et al., 1982; Sato et al., 1989, 1993) and otolith nerves (Imagawa et al., 1995, 1998) were reconstructed in serial sections. All primary vestibular afferents reaching the vestibular nuclei bifurcate into ascending and descending branches. The ascending branches mainly project to the SVN and partly to the rostral part of the MVN, whereas the descending branches mainly project to the caudal parts of the MVN and DVN, and partly to the LVN (Fig. 10). In the rostral parts of the DVN and the MVN, axon terminals are exclusively confined to the ventral region of these nuclei, whereas in the caudal parts of the DVN and MVN, terminals are distributed in both the dorsal and ventral regions. The most rostral collaterals supply terminals in the ventral part of the LVN, but none in the dorsal part of the LVN. If the distribution of MVST neurons (Fig. 8) and the distribution of axon terminals of semicircular canal nerves (Fig. 10) are compared in the vestibular nuclei, the descending branches of primary afferents arising from different semicircular canals

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Fig. 10. Dorsal view of the reconstruction of the axonal trajectory of a single horizontal semicircular nerve of irregular type in the vestibular nuclei. IVN, inferior vestibular nucleus ð¼ DVNÞ; G, genu facialis. Hached area indicates an injection site of HRP into this axon after electrophysiological identification (from Sato et al., 1989).

extensively project to the junctional area of the MVN, the DVN, and the LVN where many MVST neurons are distributed. Morphology of single vestibulospinal tract axons To visualize the intraspinal axonal trajectories of single VST axons, single MVST or LVST axons were stained intracellularly with HRP (Shinoda et al., 1986a, 1988, 1992b). Axons were penetrated in the ventral funiculus of the cervical spinal cord in the cat and were identified electrophysiologically as MVST or LVST axons by their monosynaptic responses to stimulation of the vestibular nerves and by their direct responses to stimulation of the MLF or the LVST in the medulla, respectively. Morphology of single lateral vestibulospinal tract axons. Stem axons of LVST axons run in the ipsilateral ventral funiculus. Over the stained

distances (3.4–16.3 mm), most LVST axons terminating in the cervical cord give off at least one axon collateral (Fig. 11), and up to seven collaterals per axon are observed ðmean ¼ 3:2Þ: The collaterals arise at almost right angles from the stem axons and run dorsally into the ventral horn. At the entrance into the gray matter, primary collaterals ramify into a few thick branches in a deltalike or Y-shaped configuration. The branches to the dorsomedial portion of lamina VII give rise to extensive thin branches to lamina VIII, including the ventromedial (VM) nucleus of lamina IX and the nucleus commissuralis. Terminal branches are thin (0.2–0.8 mm) with boutons en passant and one bouton at each end. Up to six boutons en passant are strung out on the last 25–50 mm of each terminal branch. The total number of boutons per collateral ranges from 38 to 262, with a mean of 161. In contrast to the wide spread of axon collaterals in the transverse plane of the spinal cord, the rostrocaudal extent of single axon collaterals is restricted, ranging from 230 to 1560 mm with an average of 760 mm (see the lower drawing of Fig. 11). There are usually gaps free of terminal boutons between terminal fields of adjacent axon collaterals, since intercollateral intervals ðmean ¼ 1490 mmÞ were much longer than the rostrocaudal extent of each terminal field. According to the degeneration study of NybergHansen and Mascitti (1964), terminals of LVST axons are not present on motoneurons in the VM nucleus in the cervical and lumbar enlargements, although LVST terminals are observed on motoneurons of the thoracic cord. In our study, terminal boutons appear to make axosomatic and axodendritic contacts with not only small- and medium-sized neurons, but also with large neurons in the VM nucleus that are probably motoneurons of axial muscles. The commissural nucleus, a cell group close to the medial border and the base of the ventral horn (lamina VIII), contains cells with their axons running across the midline in the anterior commissure (see Fig. 14). Some of these commissural neurons terminate on contralateral motoneurons (Harrison et al., 1986) (see Figs. 1B and 15B). Since a large number of terminal boutons of LVST axons are found in this nucleus, the contralateral effects following unilateral

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Fig. 11. Reconstructions of axon collaterals from a second order LVST axon at C8 labeled intracellularly with HRP. Lower diagram is a lateral reconstruction of the LVST axon at C8. Upper drawings are reconstructions in the transverse plane of B2–B4 axon collaterals shown in the sagittal plane in the lower drawing. The lower border of the central canal (CC) and the lower border of the ventral horn are indicated by the dashed lines. The arrow indicates the injection site. The stem axon could be traced further rostrally (5.9 mm from B1) and caudally (2.7 mm from B7) (from Shinoda et al., 1986a).

vestibular nucleus stimulation are probably mediated by way of this commissural connectivity (Hongo et al., 1975; Sugiuchi et al., 1992). Many boutons of LVST axons are observed in lamina VII adjacent to lamina IX in the lateral part of the ventral horn. LVST projection to this area has not been reported before, but is important, since inhibition evoked disynaptically in flexor motoneurons from Deiters’ nucleus (Grillner et al., 1970) is mediated by Ia inhibitory neurons located in this area (Jankowska and Lindstroem, 1972) (see Fig. 15B). Morphology of single medial vestibulospinal tract axons. MVST axons are classified into two groups, crossed and uncrossed MVST axons,

which descend in the spinal cord contralateral and ipsilateral to their cell bodies, respectively. Stem axons of MVST neurons run in the mediodorsal portion of the ventral funiculus. The branching pattern of MVST axons is very similar to that of LVST axons, but different from that of CST and RBST axons (Futami et al., 1979; Shinoda et al., 1982, 1986a, 1988, 1992b). One to seven axon collaterals are seen for individual MVST axons (Shinoda et al., 1988). Both uncrossed and crossed MVST axons have many common features regarding the branching pattern and terminal distribution. A typical example of an uncrossed MVST axon is illustrated in Fig. 12. In this axon, nine axon collaterals arise from a stem axon at almost right angles. Primary collaterals

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Fig. 12. Reconstruction of an uncrossed second-order MVST axon filled with HRP in the transverse plane (left) and in the horizontal plane (right) at C2–C3 segments of the cat spinal cord. Seven axon collaterals were given off at almost right angles from a stem axon to the motor nucleus in lamina VIII just dorsomedial to the ventromedial nucleus (VM) and one collateral to the nucleus spinalis n. accessorii (A). Note that a single MVST axon innervates multiple motor nuclei of neck muscles (from Shinoda et al., 1992b).

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run laterally and enter into the ventral horn at its medial border. They divide into several thick branches immediately after the entrance to the ventral horn and spread in a delta-like fashion in the transverse plane. Those branches are classified into three groups in terms of their course and destination (Fig. 13). One group of branches run ventrolaterally into the VM nucleus and gives rise to extensive terminal arborizations there. Some of them further extend into the accessorius (A) nucleus. A second group of branches projects laterally to the A nucleus or its adjacent lamina VIII. On their way, thin branchlets are given off to lamina VIII dorsal to the VM nucleus. A third group of branches runs dorsolaterally, emitting thin branchlets on their way and terminating in the medial portion of the dorsal lamina VIII and its adjacent lamina VII. Each MVST axon does not always have these three groups of branches and usually lacks one or two groups. In contrast to the wide extent of terminal arborization in the transverse plane, the rostrocaudal extent of single axon collaterals is restricted (see Fig. 12, right), ranging from 300 to 2100 mm with a mean of 620 mm. Since the average distance between adjacent primary collaterals (1870 mm) is much wider than the rostrocaudal extent of single axon collaterals, there are usually gaps free of terminal boutons between the terminal fields of adjacent axon collaterals. The terminal area of MVST axons occupies lamina IX, including both the VM and the A nuclei, lamina VIII, including the commissural nucleus and lamina VII, including the central cervical nucleus. Terminal boutons are most predominant in lamina IX, especially in the VM nucleus, and axosomatic and axodendritic contacts are observed on large, medium, and even small cells (Fig. 13, arrowheads) (Shinoda et al., 1992b). The VM nucleus contains motoneurons of neck extensors (Mm. dorsi proprii) and the A nucleus contains motoneurons of neck flexors such as the sternocleid muscle (Sugiuchi and Shinoda, 1992). To confirm that MVST axons indeed make contact with motoneurons in lamina IX, motoneurons innervating different neck muscles were retrogradely labeled with HRP (Shinoda et al., 1988). Some boutons of MVST axons were observed on cell bodies or proximal dendrites of labeled motoneurons

and others of the same MVST axons seemed to make contact with cell bodies or proximal dendrites of unlabeled but large counterstained cells in a different portion of the VM nucleus. About one-third of the examined MVST axons projected to both the VM and the A nuclei, and presumed axodendritic contacts were observed on large neurons in each nucleus. These findings give morphological support for single VST axons innervating motoneurons of different neck muscles simultaneously.

Morphology of single commissural interneurons mediating vestibular input to neck motoneurons Neck motoneurons receive inputs from bilateral vestibular labyrinths and the shortest connections between vestibular primary afferents and neck motoneurons are disynaptic (Wilson and MelvillJones, 1979). In the lumbar spinal cord, extensor motoneurons receive bilateral vestibular inputs (Fig. 15B) and contralateral vestibular input is considered to be mediated via commissural neurons (CNs) in the spinal cord (see also Fig. 1B, right) (Aoyama et al., 1971; Hongo et al., 1975). CNs in lamina VIII in the lumbar cord were well analyzed as to their targets, locations and peripheral somatosensory inputs (Harrison et al., 1986; Jankowska and Noga, 1990), but CNs in the cervical cord have not been well understood. There are cervical neurons outside the motor nuclei that receive vestibular input (Hirai et al., 1979; Schor et al., 1986; Alstermark et al., 1987). Whether these neurons terminate on neck motoneurons remained to be unknown. The location of CNs in the upper cervical cord was identified in the medial half of lamina VIII by localized injection of a fluorescent dye in the ventral horn (Bolton et al., 1991). To identify CNs that convey vestibular inputs to contralateral neck motoneurons, axons were penetrated in the dorsomedial portion of the ventral funiculus near the central canal in the cat, and were presumed to be axons of CNs, when they were activated di- or trisynaptically by stimulation of the contralateral vestibular nerve (Sugiuchi et al., 1992, 1995). Twenty-two axons were regarded electrophysiologically as CNs and injected with HRP. The location of their cell bodies almost

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Fig. 13. Camera lucida drawings of synaptic boutons of uncrossed MVST axons in transverse sections at C2. Lower left and upper middle diagrams: Terminal arborizations in lamina IX [Nucl. spinalis n. accessorii (larger square) and nucl. dorsomedialis (smaller square)] of the axon collaterals shown in the inset on the upper left. Lower right diagrams: Terminal arborizations in lamina IX (nucl. ventromedialis) of the axon collateral shown in the inset on the upper right. Arrowheads in each diagram indicate apparent synaptic contacts with counterstained cells. A, nucleus spinalis n. accessorii; Ce, nucleus cervicalis centralis; VM, nucleus ventromedialis (from Shinoda et al., 1992b).

corresponds to the medial two-thirds of laminae VIII and VII of Rexed, but they are distributed much more widely than in the commissural nucleus defined by Rexed (1954). The stained CNs are multipolar and small to large in size. A typical example of the branching pattern of a CN is shown in Fig. 14. The stem axon originating from the cell body runs medially in a transverse plane without a collateral and crosses the midline through the anterior commissure. Then, it bifurcates into ascending and descending main branches and they run in the dorsomedial portion of the ventral funiculus. Multiple axon collaterals are

given off at almost right angles from both main branches. In this neuron, eight collaterals arise from the ascending branch at C1 and C2, and seven collaterals from the descending branch at C3 at irregular intercollateral intervals. Most CNs have multiple axon collaterals and the number of axon collaterals stained per neuron is 3–15 with an average of 6.4. The rostrocaudal extension of individual axon collaterals is very narrow (230–1300 mm), whereas the distances between adjacent primary axon collaterals are much wider (385–5460 mm) (Fig. 14, left). Axon terminals of each primary collateral are fairly localized in the

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Fig. 14. Reconstruction of a single commissural neuron receiving disynaptic excitatory input from the labyrinth. The cell body was located at the junction between C2 and C3. The left inset shows the dorsal view of the reconstructed axonal trajectory of this neuron in the upper cervical spinal cord. Letters R and C attached by numbers represent rostral and caudal axon collaterals numbered from the stem axon, respectively. Individual collaterals are shown in representative transverse sections of the cervical cord (from Sugiuchi et al., 1992).

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Fig. 15. Nuclear distribution, pathways, and synaptic nature of vestibular output neurons innervating ocular and spinal motoneurons (A) (see the details in the text). VN, vestibular nucleus; S, M, L, and D, superior, medial, lateral, and descending vestibular nucleus, respectively; MLF, medial longitudinal fasciculus; BC, brachium conjunctivum; MN, motoneuron. (B) Vestibular influences on flexor and extensor motoneurons of limb muscles. Ia, Group Ia fiber arising from a muscle spindle, IaIN; Ia inhibitory interneuron for reciprocal inhibition, contra FRA; contralateral flexor reflex afferents for withdrawal reflex. Open neurons are excitatory and closed neurons are inhibitory (modified from Grillner and Hongo, 1972).

ventral horn and mainly distributed in lamina IX and its adjacent lamina VIII but sometimes in lamina VII. Terminal boutons are predominantly distributed in the VM and dorsomedial nuclei (Sugiuchi et al., 1992). In each CN, terminal arborizations of most axon collaterals are located in similar areas in lamina IX. In the neuron of Fig. 14, adjacent axon collaterals converged into the common ventromedial areas of the ventral horn and those areas are arranged in a longitudinal direction of the spinal cord over two segments. Axon terminals of the CNs really make apparent contact with neck motoneurons labeled retrogradely with HRP. These findings indicate that

CNs serve as a relay from the labyrinth to neck motoneurons. Our later study showed that motoneurons of some neck muscles receive trisynaptic inhibitory input from the contralateral anterior canal nerve (Shinoda et al., 1997). Such an example is shown in a motoneurons of M. obliquus capitis caudalis (see Fig. 20 for an example). Stimulation of the commisural nucleus in the upper cervical cord evoked monosynaptic inhibition in motoneurons of this neck muscle. Furthermore, some of the CNs are only activated by ipsilateral rotation for anterior-canal stimulation and ipsilateral electrical vestibular stimulation, and terminate on contralateral neck motoneurons. Taken together, these

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findings indicate that these CNs are inhibitory interneurons mediating the anterior canal input to contralateral neck motoneurons (Sugiuchi et al., 1995). This is the first example of commissural neurons that are identified as inhibitory in the spinal cord. Contralateral utricular input to neck motoneurons is known to be inhibitory (Bolton et al., 1992). This effect may be mediated by CNs, although there is a possibility of RST neurons responsible for that. CNs in lamina VIII in the lumbar cord are known to be excitatory in a crossed extensor reflex pathway (Harrison et al., 1986). The possibility that there are excitatory CNs in the upper cervical cord remains to be determined. Functional connections of vestibular neurons with ocular motoneurons and spinal neurons It has been well known that activation of the labyrinth leads to various postural reflexes. Rotation of an animal to one side causes the head turning to the opposite direction and nose-down tilting of an animal causes dorsal flexion of its head. Both head movements lead to restoration of the head’s position in space. These effects are also exerted on other axial and limb muscles, so that these labyrinthine reflexes as a whole result in stabilization of head and eye positions and finally of the visual field. Figure 15A is a summary diagram of the organization of vestibulospinal and vestibuloocular neurons and their target motoneurons. It has long been known that stimulation of Deiters’ nucleus (the lateral vestibular nucleus) increases activity of extensor muscles (Brodal et al., 1962). Lund and Pompeiano (1968) first showed that this increase was due to monosynaptic excitation in some hindlimb motoneurons. Later, Grillner et al. (1970) demonstrated that stimulation of the Deiters’ nucleus produced via the LVST mono- and disynaptic excitation in a-extensor motoneurons and di- and trisyanaptic inhibition in flexor motoneurons of hindlimb muscles (Fig. 15B). This inhibition is mediated by Group Ia inhibitory interneurons. The Deiters’ nucleus also has an influence, via the LVST, on neck and back motoneurons (Wilson and Yoshida, 1969; Akaike et al., 1973). Stimulation of the vestibular nuclei revealed that the MVST makes monosynaptic connections with neck motoneurons and contains inhibitory

fibers (Wilson and Yoshida, 1969). When Eccles and his colleagues (Eccles, 1964) discovered inhibitory neurons in the nervous system, most researchers tacitly assumed that inhibitory neurons were interneurons with short axons. However, Wilson and his colleagues first showed that some of the vestibulospinal neurons with long axons are inhibitory. Subsequently, Akaike et al. (1973) showed that the MVST contains excitatory fibers. This inhibition of neck motoneurons by MVST axons is blocked by intravenous injection of strychnine, but not of bicuculline or picrotoxin, suggesting that the involved transmitter seems to be glycine rather than GABA (Felpel, 1972). Since these pioneering studies of the vestibular nuclei on motoneurons of various parts of the body, extensive analysis has been made on influences of semicircular canal nerves on neck motoneurons (Wilson and Maeda, 1974; Uchino et al., 1988, 1990; Uchino and Isu, 1992a, b; Shinoda et al., 1994, 1997; see Ito, 1984 for vestibular influences on ocular motoneurons). In the following, vestibular influences on neck motoneurons will be summarized in relation to their effects on spinal and ocular motoneurons in a rather generalized form. All LVST neurons are excitatory, whereas MVST neurons are both excitatory and inhibitory (see the details in Wilson and Melvill-Jones, 1979). Vestibuloocular neurons (VONs) and vestibulocollic neurons (VCNs) innervating contralateral motoneurons are excitatory and those innervating ipsilateral motoneurons are inhibitory. However, there are some exceptions; some VCNs receiving a posterior canal input inhibit contralateral neck motoneurons or excite ipsilateral neck motoneurons. Most excitatory MVST neurons have axon collaterals projecting to ocular motoneurons, although some excitatory VONs and VCNs project only to ocular motoneurons or neck motoneurons, respectively. Inhibitory VONs innervating vertical ocular motoneurons are located in the SV, whereas inhibitory VCNs are in the MVN, indicating that single inhibitory VN neurons could not simultaneously project to ocular motoneurons and neck motoneurons (Isu et al., 1991). There is one exception for this that single inhibitory MVN neurons project to abducens motoneurons and neck motoneurons (not illustrated).

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Morphology of single reticulospinal axons To analyze the axonal trajectories of single RST axons, we selected RST neurons that receive input from the SC. These neurons are known to be involved in neck movements in orienting behavior (Grantyn and Berthoz, 1987). Axons were penetrated in the ventromedial funiculus between C1 and C2 and presumed to be RST axons, when spikes were evoked monosynaptically without any trace of postsynaptic potentials by stimulation of the contralateral superior colliculus (SC) (Kakei et al., 1994). The latencies of the spikes ranged from 1.0 to 1.5 ms (n ¼ 15; mean
SD; 1:3
0:2 ms) and these spikes were regarded as being evoked monosynaptically (Peterson et al., 1974; Grantyn and Berthoz, 1987; Iwamoto et al., 1990). All stained axons were electrophysiologically identified as not projecting below T2, since no antidromic responses were evoked by stimulation at T2. In 10 of 15 axons injected with HRP, cell bodies of origin were retrogradely identified in the nucleus reticularis pontis caudalis (NRPC) (see an upper right inset in Fig. 15, arrow). The axons were stained over the distance ranging from 13 to 25 mm rostrocaudally at C1–C3 ðn ¼ 1lÞ: A typical example of the branching pattern of a single RST neuron in the cervical cord is shown in Fig. 16. A stem axon runs in the ventromedial funiculus and gives rise to multiple axon collaterals at almost right angles over a few cervical segments. Each collateral ramifies three to five times, and mainly spreads in a frontal plane in the ventral horn. The number of axon collaterals stained per neuron is 2–11 with an average of 5.4. The rostrocaudal extension of individual axon collaterals is relatively narrow (400–2500 mm, mean ¼ 900 mm) compared to much wider intercollateral intervals (300–800 mm, mean ¼ 2200 mm). Therefore, there are usually gaps free of axon terminals between adjacent axon collaterals. Axon terminals of each primary collateral are localized in the ventral horn and mainly distributed in laminae IX and VIII, and sometimes in lamina VII of Rexed (Rexed, 1954) (Fig. 16, middle). Terminal boutons are predominantly distributed in or very close to neck motor nuclei, and some of them appear to make contact with retrogradely labeled neck motoneurons

(Fig. 16, arrows in the middle column). In the neuron of Fig. 16, collateral 2 appears to make contact with a motoneuron of the complexus muscle, and collateral 3 appears to make contact with an accessorius motoneuron. Out of nine RST axons with a projection to neck motor nuclei, eight axons (90%) project to multiple neck motor nuclei (n ¼ 2–5). These results indicate that single RST axons mediating SC input to the cervical spinal cord project to multiple neck motor nuclei and may control activity of multiple muscles simultaneously. The axons sampled, mentioned above, are monosynaptically activated by stimulation of the contralateral SC. These axons may be either RST axons (Peterson et al., 1974; Grantyn and Berthoz, 1987; Iwamoto et al., 1990) or spinal interneurons innervated by TST neurons (Alstermark et al., 1987). In the above sample, stained stem axons of larger diameters are always traced rostrally to the medulla, indicating that they do not originate from spinal interneurons. Furthermore, retrogradely labeled cell bodies are mostly found in the NRPC ipsilateral to the stained intraspinal stem axons. Therefore, all of these axons should be considered as RST axons. The NRPC receives strong projection from the SC (Huerta and Harting, 1982), and densely projects to motor nuclei innervating axial muscles as well as laminae VII and VIII (Holstege and Kuypers, 1982). Using an intracellular recording technique, Anderson et al. (1971) demonstrated that the SC exerts an excitatory action on contralateral neck motoneurons disynaptically. They further suggested that most of this action was due not to the TST but to tecto-reticulo-spinal pathways. This pathway was confirmed by Iwamoto and Sasaki (1990) using a spike triggered averaging technique.

The tectospinal tract Morphology of single tectospinal axons To visualize intra-axonal trajectories of single TST neurons, axons were penetrated in the ventral funiculus between C1 and C2, and identified as TST axons by their direct responses to stimulation of the contralateral SC (Muto et al., 1996). After the axons were identified as TST axons, they were

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Fig. 16. Reconstruction of a single reticulospinal tract (RST) neuron receiving monosynaptic excitatory input from the superior colliculus (SC). Left inset shows dorsal view of reconstructed axonal trajectory of this neuron in the upper cervical spinal cord. An arrow indicates an injection site. Numbers 1–5 represent individual collaterals which are shown in representative transverse sections of the spinal cord on the right. Broken lines indicate individual motor nuclei identified by retrograde labeling of neck motoneurons. Only motoneurons contacted by this RST neuron are depicted and indicated by arrows. The cell body is located in the nucleus reticularis pontis caudalis (NRPC) (top right: arrow). ACC, nucleus spinalis n. accessorii; COMP, motor nucleus of the complexus; FLEX, motor nucleus of neck flexor, SPL, motor nucleus of the splenius; OCA, motor nucleus of the obliquus capitis caudalis. VN, vestibular nucleus; genu, genu facialis; MLF, medial longitudinal fasciculus (from Kakei et al., 1994).

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injected with HRP iontophoretically. Their cell bodies (arrow in Fig. 17) were successfully stained retrogradely and identified in the intermediate and deep layers in the caudal two-thirds of the contralateral SC. Stem axons of TST neurons give rise to multiple axon collaterals at C1 and C2 segments (Fig. 17). When viewed in the horizontal plane, primary axon collaterals arise at a more-or-less right angle from stem axons. These collaterals run in the ventral funiculus for some distances without branching or after bifurcating once, the primary or secondary collaterals enter the ventral horn at its medial border. The maximum number of collaterals for a single TST axon is 7 ðmean ¼ 2:7Þ: The distances between branching points of adjacent primary collaterals from a stem axon range from 400 to 7700 mm with an average of 2600 mm. The rostrocaudal extension of individual well-stained axon collaterals range from 200 to 3100 mm ðmean ¼ 700 mmÞ in the spinal gray matter. Since intercollateral intervals are usually wider than rostrocaudal spreads of individual axon collaterals, there are gaps free of axon terminals between adjacent axon collaterals. After the entrance into the gray matter, some collaterals run dorsolaterally, passing through lamina IX without any terminal branches, and ramify within the lateral parts of laminae V–VIII (Fig. 17, collaterals 2–6), whereas other collaterals run dorsolaterally to the lateral parts of laminae VI–VIII and on their way give rise to a number of terminal branches in lamina IX. Most collaterals ramify mainly in the transverse plane and have simple structures (Fig. 17, collaterals 2, 6, and 7). Some other collaterals ramify a few times in the gray matter, while giving rise to a number of short side branchlets that bear some swellings (Fig. 17, collateral 4). Most short terminal branches with a few en passant swellings and one terminal swelling terminate near the parent branch. The number of swellings per collateral is small, ranging from 10 to 326 ðmean ¼ 65:4Þ: Among the long descending motor tract axons examined, TST axons have the least extensive axonal arborizations and their axon collaterals have the simplest structures in the spinal cord. The total number of axon collaterals arising from each long descending tract axon cannot be determined

due to technical limitations, but TST axons seem to have the smallest number of axon collaterals among the long descending motor tract axons of the medial group. Single TST axons seem to be classified into two groups, depending on the amount of their projection to lamina IX. One group of TST axons have a considerable projection to lamina IX besides the slightly stronger projections to the lateral parts of laminae VI–VIII, whereas the other group of TST axons project mainly to the lateral parts of laminae VI–VIII with little or no projection to lamina IX. Synaptic contacts with retrogradely labeled neck motoneurons could be detected in none of 12 TST axons examined, but many axon terminals seemed to make contacts with counterstained neurons in the lateral parts of laminae V–VIII.

Morphology of single spinal interneurons receiving monosynaptic excitation from the superior colliculus Almost all TST axons have a common projection area in the lateral parts of lamina VII, VIII, or both. Interneurons in these laminae receive monosynaptic excitation from the contralateral SC (spikes are evoked at latencies shorter than 1.4 ms and latencies of evoked spikes are fluctuating). Figure 18 shows a typical example of such an interneuron in lamina VIII (Muto et al., 1996). This neuron with dendrites radiating in the frontal plane has a stem axon running caudally almost in parallel with the midline at the depth of around 3 mm in the ventral funiculus, and gives rise to multiple primary collaterals at almost right angles at C1 and C2. These collaterals ramify in a delta-like fashion in the ventral horn and terminate in laminae VII–IX. Two most rostral collaterals project contralaterally through the anterior commissure, and terminate mainly in lamina VIII and only slightly in lamina IX. Compared with the collaterals of the TST axons, the collaterals of this interneuron project extensively to lamina IX, and far less to the lateral parts of laminae VII and VIII. In lamina IX, axon terminals of this interneuron appear to make contacts with cell bodies and proximal dendrites of retrogradely labeled neck motoneurons in the ventrolateral part of lamina IX (probably the neck extensor motor nucleus)

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Fig. 17. Reconstructions of a tectospinal tract (TST) axon in the transverse plane (right) and in the horizontal plane (left) at C1 and C2. The numbers attached to individual collaterals correspond to those in the horizontal reconstruction on the left. This axon projects to the dorsomedial part of lamina IX, spinal accessory nucleus (Acc) and laminae V–VIII of Rexed. Its cell body is located in the lateral part of the intermediate layer in the contralateral middle-third of the SC as indicated by an arrow (upper middle inset). Broken lines indicating the border of lamina IX are drawn based on the distribution of retrogradely labeled neck motoneurons after HRP injection into the ventral roots of C1 and C2 (from Muto et al., 1996).

(Fig. 18B) and the A nucleus (Fig. 18A). The fourth, seventh, and ninth collaterals of the same interneuron have also axon terminals in the ventromedial part of lamina IX where neck flexor motoneurons are located. As in this example, single TST axons may exert their strong influences

onto motoneurons of multiple neck muscles via interneurons in laminae VII and VIII. Anderson et al. (1971) showed in an electrophysiological study that the pathways arising in the deep layers of the SC exert a disynaptic excitatory action on contralateral neck motoneurons.

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Fig. 18. Reconstructions of a spinal interneuron receiving monosynaptic excitation from the contralateral SC. The cell body is located in lamina VIII at C1 (top middle). The first two collaterals project to the contralateral side. Note that collaterals of the interneuron project more specifically to neck motor nuclei than TST axon collaterals. Lower right inset diagrams A and B are the enlarged view of the regions indicated by arrows A (nucleus spinalis n. accessorii) and B (motor nucleus of the complexus muscle), respectively. All neurons shown in the inset diagrams are retrogradely labeled neck motoneurons. Arrowheads show apparent contacts of the synaptic boutons with retrogradely labeled neck motoneurons (from Muto et al., 1996).

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In their study, the MLF was cut at the caudal medullary level on the side contralateral to the SC stimulation. This lesion was expected to interrupt the bulk of crossed TST axons. Since the lesion had no consistent effect on the amplitude of contralateral EPSPs, they concluded that a majority of the excitatory action was due not to the TST, but to the tecto-reticulo-spinal pathway. On the other hand, the above anatomical data indicate that some of these disynaptic EPSPs must be relayed to neck motoneurons via cervical interneurons activated by TST axons. Since TST fibers run not only in the MLF, but also in the medullary reticular formation lateral to the MLF, the section of the MLF might not eliminate all the TST fibers to the cervical cord. Therefore, the presence of disynaptic EPSPs after sectioning the MLF does not necessarily indicate that the remaining disynaptic responses are relayed through the tecto-reticulo-spinal pathway, but suggests that the TST probably exerts a considerable effect on neck motoneurons via spinal interneurons during head movements.

Functional connections of medial long descending motor tracts with neck motoneurons Figure 19 summarizes electrophysiological properties of medial long descending motor tract neurons on neck motoneurons. VST influences on neck motoneurons are excluded from this diagram, since they were described in the previous section. When an interesting object appears in the visual field, animals quickly move both eyes and a head to that interesting object. This behavior is called an orienting response, and the SC is a primary center for orienting (Hess, 1956; Sprague and Meikel, 1965). The tecto-reticulo-spinal system is mainly involved in the control of orienting head movements (Anderson et al., 1971). Output neurons in the intermediate and deeper layers of the caudal part of the SC project through the predorsal bundle to contralateral reticulospinal neurons (RSNs). Those RSNs that terminate on neck motoneurons usually receive convergent inputs from the contralateral SC and motor cortex. Such RSNs are functionally grouped into two groups, and are distributed in two parts of the reticular

Fig. 19. Schematic diagram showing effects of different medial long descending tracts on neck motoneurons. Mx, motor cortex; FFH, the nucleus of the fields of Forel; SC, superior colliculus; NRPC, nucl. reticularis pontis caudalis; NRC, nucl. reticularis gigantocellularis (for references, see the text).

formation; the nucleus reticularis pontis caudalis (NRPC) and the nucleus reticularis gaigantocellularis (NRG) (Alstermark et al., 1985, 1992a, b, c; Iwamoto and Sasaki, 1990; Iwamoto et al., 1990). RSNs in the NRPC receive stronger input from the SC than from the motor cortex (Mx), whereas RSNs in the NRG receive stronger input from the Mx than from the SC. The majority of these RSNs projecting to neck motoneurons continue their projections to the lower cervical cord (the brachial segmental level), although they do not project to the lumbar cord. In addition to the tecto-reticulospinal system, tectal influences are also exerted by

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way of the tectospinal (TS) tract. TS axons run in the contralateral MLF in the brainstem and have abundant collaterals to the NRPC and the NRG (Grantyn et al., 1992, 2004), probably terminating on RSNs there. They further run in the ventromedial funiculus in the spinal cord and excite neck motoneurons via spinal interneurons (Muto et al., 1996). Another pathway from the SC involved in orienting head movements is the interstitiospinal (IS) tract. Neurons in the nucleus of the fields of Forel receive input from the ipsilateral SC and project monosynaptically or disynaptically via the NRG to ipsilateral neck motoneurons (Holstege and Cowie, 1989; Isa and Sasaki, 1992a, b) and this pathway is considered to be related to vertical head movements. These findings indicate that orienting commands from the SC for head movements are transmitted to neck motoneurons by way of multiple medial long descending motor tract pathways.

Functional roles of multiple axon collaterals of single long descending motor tract axons Head position control is an ideal paradigm for studying how the CNS controls a multidimensional motor system (Richmond and Vidal, 1988; Graf et al., 1997). Head-movement signals detected by the semicircular canals are mediated through vestibulocollic pathways that link each of the three semicircular canals to a set of neck muscles. For tasks necessitating compensatory head movements, the CNS programs muscle-activation patterns in a synergy, i.e., in a specific spatial and temporal combination rather than an infinite variety of patterns of contracted muscles. Stimulation of individual semicircular canals produces canalspecific head movements (Suzuki and Cohen, 1964). The plane of the head movement produced by canal stimulation parallels that of the stimulated canal, i.e., they are almost coplanar. Therefore, a signal from each semicircular canal must be distributed to an appropriate set of neck muscles in order to induce compensatory head movement in the same plane as the plane of the stimulated canal. Obviously, this process is more economical when a given descending motor command signal is

distributed by a single neuron with divergent branches to different target motoneurons that participate in cocontraction of multiple muscles to produce the required movement. Since the pioneering work by Wilson and Maeda (1974), the convergence of different canal nerve inputs onto single motoneurons has been extensively analyzed in the vestibulocollic system (Wilson and MelvillJones, 1979), but its converse, divergent properties of VST axons, have not attracted much attention. As shown in section ‘‘Morphology of single vestibulospinal tract axons,’’ virtually all of single VST axons have multiple axon collaterals at different spinal segments and terminate on motoneurons of different neck muscles. The important question arises as to whether the branching pattern of an individual descending motor tract axon including a VST axon reveals if it innervates different motor nuclei randomly or selectively; i.e., the assumption is that a combination of motor nuclei of a specific set of functionally relevant neck muscles would be innervated by individual long descending motor axons. We tested for the implementation of a functional synergy of neck muscles by even single, long descending motor tract neurons. This issue was addressed in the vestibulocollic system first and then in the tectoreticulospino-collic system. We first analyzed input patterns from the six semicircular canals to motoneurons of 10 different neck muscles by recording intracellular potentials from neck motoneurons while stimulating individual semicircular canal nerves (Shinoda et al., 1994, 1996, 1997). Figure 20 shows an example of semicircular canal input patterns in six neck muscles. This diagram shows convergent input patterns from six semicircular canals to individual neck muscles. But our purpose of this series of the experiments was to reveal the divergent output pattern from a particular semicircular canal to motoneurons of different neck muscles. For example, an excitatory output from the horizontal semicircular canal is conveyed via the contralateral MVST to motoneurons of all six neck muscles on the contralateral side, whereas an inhibitory output from the horizontal semicircular canal is conveyed via the ipsilateral MVST to motoneurons of all six neck muscles on the ipsilateral side. However, an inhibitory output

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Fig. 20. Convergent input patterns and pathways from the six semicircular canals to motoneurons supplying six different neck muscles. Open circles and closed circles represent neurons that are excitatory and inhibitory, respectively. The key feature of this figure is that all the motoneurons supplying each neck muscle had a homogeneous pattern of input from the six semicircular canals. Note that this diagram shows convergent input patterns from the six semicircular canals to each neck muscle, but at the same time divergent output patterns from a particular semicircular canal to six neck muscles. A, H, and P, anterior, horizontal, and posterior semicircular canal nerves, respectively; MN, neck motoneurons; MLF, medial longitudinal fasciculus. M. rectus cap. dor., M. rectus capitis dorsalis; M. obli. cap. caud.; M. obliquus capitis caudalis (from Sugiuchi et al., 2004).

from the posterior semicircular canal is conveyed via the ipsilateral MVST to motoneurons of all neck muscles except M. obliquus capitis caudalis. In this way, we could determine the output patterns from individual semicircular canals to all 10 neck muscles. As a next step, we assumed that these spatial innervation patterns of individual semicircular canals over neck muscles should be determined by branching patterns of individual VST neurons in neck motor nuclei. To confirm this

assumption, we analyzed the intraspinal branching patterns of single MVST neurons after identifying from which semicircular canal those neurons received input physiologically. MVST axons were impaled by a microelectrode inserted into the ipsilateral or contralateral MLF. They were identified as VST axons by their monosynaptic responses to stimulation of primary vestibular afferents. Then the axon’s maximal response to head rotations was determined on a three-dimensional turntable

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(Shinoda et al., 1988, 1992b), and each axon was then classified in terms of the semicircular canal input it received, i.e., the lateral, anterior or posterior canal related MVST axons. As an example of the above experimental approach, we discuss below the properties of MVST axons receiving input from the ipsilateral posterior canal and projecting to ipsilateral neck motor nuclei (Sugiuchi et al., 2004). After the abovementioned physiological identification, such axons were injected with HRP in the upper cervical cord where two to three motor nuclei were retrogradely labeled with HRP. These axons run in the ipsilateral MLF, and they commonly exhibit a stereotypic innervation of the motor nuclei of (1) the sternomastoid–cleidomastoid muscles, (2) the semispinalis group (i.e., the biventer and complexus muscle), and (3) the multifidus group (i.e., the multifidus cervicis and rectus capitis dorsalis muscle). Each single collateral of these MVST axons does not necessarily terminate within all of these motor nuclei, but single posterior canal related MVST axons innervate the above group of the motor nuclei by way of multiple collaterals. This spatial innervation pattern over the neck motor nuclei tested is found in almost all of the posterior canal related, uncrossed MVST axons examined. Posterior canal related VST neurons include both excitatory and inhibitory neurons (Isu et al., 1988, 1990). The excitatory neurons send their axons either contralaterally into the MLF or ipsilaterally in the LVST. These posterior canal-related VST axons passing in the ipsilateral MLF are most likely inhibitory to their target motoneurons (Shinoda et al., 1994, 1997; Sugiuchi et al., 2004), since posterior canal related excitatory VST axons that project ipsilaterally are LVST axons innervating motoneurons of the obliquus capitis caudalis muscle (Shinoda et al., 1994, 1997; Sugiuchi et al., 2004). Indeed, electron microscopic analysis of some HRP-labeled axon terminals of these VST axons has demonstrated that their terminals have morphological characteristics of inhibitory synapses with obliquus capitis caudalis motoneurons. We further tried to specify functional synergies among neck muscles that were innervated by single MVST axons, which responded to input from other semicircular canals. The posterior canal

on one side is coplanar to the anterior canal on the opposite side. The abovementioned posterior canal related ipsilaterally projecting MVST axons are inhibitory to the abovementioned group of muscles. We also found that contralaterally projecting excitatory MVST axons receiving input from the anterior semicircular canal terminated in the same group of neck motor nuclei. In other words, this result indicated that single MVST axons receiving input from either one of these pairs of coplanar canals exerted their influence on the same functional set of neck muscles, but with opposite effects. In summary, it was shown that single MVST axons receiving input from a particular semicircular canal have a common pattern of projection onto the motoneurons of a set of neck motor nuclei that are proper for that semicircular canal. Furthermore, the MVST axons’ innervation patterns clearly explain the electrophysiologically determined output patterns from individual semicircular canals to motoneurons supplying functionally related sets of neck muscles. The SC is known to be an important center for the control of coordinated eye–head (orienting) movements. Electrical stimulation of the SC elicits coordinated eye and head movements toward a target, with the orientation direction dependent on the specific site of intra-SC stimulation. Thus, the output signals of the SC should contain specific information on which neck muscles should be co-activated. Collicular influences onto neck motoneurons are conveyed via TS axons and also by RSNs. A key question is whether the functional synergy controlled by the SC is the same or different as that controlled by the vestibulospinal system, namely, whether a single RSN may implement the same functional synergy for head movements as a single VST neuron. RST axons receiving SC input have multiple axon collaterals and made contact with retrogradely labeled motoneurons supplying different neck muscles (Kakei et al., 1994). We interpret this result as meaning that RST axons simultaneously mediate output from the SC to motoneurons supplying functionally related different groups of neck muscles. Furthermore, many RST axons innervate the same group of neck motor nuclei as do the posterior

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canal related MVST axons. This finding strongly suggests that branching patterns of single RST axons are similar to those of single MVST axons, and that both single MVST and RST axons may have similar innervation patterns for neck muscles, thereby controlling the same functional sets of these muscles. In this chapter, we mainly described our data on the divergent properties of single, long descending motor-tract neurons in the spinal cord. These data provide evidence that single motor-tract neurons are implicated in the neural implementation of functional synergies for head movements. Our results further show that single MVST neurons receiving a particular canal input innervate a functional set of multiple neck muscles, and thereby implement a canal-dependent, head-movement synergy. Additionally, both single MVST and RST axons may have similar innervation patterns for neck muscles, and thereby control the same functional sets of neck muscles. This finding may lead to a conclusion that the tecto-reticulo-collic system uses semicircular-canal coordinates for control of neck movements. In order to stabilize redundant control systems in which many muscles generate force across several joints, the CNS routinely uses a combination of a control hierarchy and sensory feedback. In addition, in the head-movement system, the elaboration of functional synergies among neck muscles is another important strategy to stabilize the system, because it helps to decrease the degrees of freedom in this particularly complicated control system. Abbreviations CN CNS CST DVN HRP IST LVN LVST MLF MVN MVST NRPC

commissural neuron central nervous system corticospinal tract descending vestibular nucleus horseradish peroxidase interstitiospinal tract lateral vestibular nucleus lateral vestibulospinal tract medial longitudinal fasciculus medial vestibular nucleus medial vestibulospinal tract nucleus reticularis pontis caudalis

RBST RST SA SC TST VM VST

rubrospinal tract reticulospinal tract nucleus spinalis n. accessorii superior colliculus tectospinal tract nucleus ventromedialis vestibulospinal tract

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