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Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013.

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Anatomy and Physiology of the Spinal Cord

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Anatomy of the Spinal Cord

Gross Anatomy

The spinal cord is part of the central nervous system (CNS), which extends caudally and is protected by the bony structures of the vertebral column. It is covered by the three membranes of the CNS, i.e., the dura mater, arachnoid and the innermost pia mater. In most adult mammals it occupies only the upper two-thirds of the vertebral canal as the growth of the bones composing the vertebral column is proportionally more rapid than that of the spinal cord. According to its rostrocaudal location the spinal cord can be divided into four parts: cervical, thoracic, lumbar and sacral, two of these are marked by an upper (cervical) and a lower (lumbar) enlargement. Alongside the median sagittal plane the anterior and the posterior median fissures divide the cord into two symmetrical portions, which are connected by the transverse anterior and posterior commissures. On either side of the cord the anterior lateral and posterior lateral fissures represent the points where the ventral and dorsal rootlets (later roots) emerge from the cord to form the spinal nerves. Unlike the brain, in the spinal cord the grey matter is surrounded by the white matter at its circumference. The white matter is conventionally divided into the dorsal, dorsolateral, lateral, ventral and ventrolateral funiculi. Each half of the spinal grey matter is crescent-shaped, although the arrangement of the grey matter and its proportion to the white matter vary at different rostrocaudal levels. The grey matter can be divided into the dorsal horn, intermediate grey, ventral horn and a centromedial region surrounding the central canal (central grey matter) The white matter gradually ceases towards the end of the spinal cord and the grey matter blends into a single mass (conus terminalis) where parallel spinal roots form the so-called cauda equina.1

The dorsal roots leave the dorsal horn and dorsolateral white matter, coalesce into two bundles and enter the dorsal root ganglion (DRG) in the intervertebral foramen. Immediately distal to the ganglion, the dorsal and ventral roots unite and form a trunk, the spinal nerve. The spinal nerves, which are now outside the vertebral column, converge and form plexuses and from these emerge the peripheral nerves. The number of spinal nerves and spinal segments largely corresponds to the number of vertebrae with a few exceptions: there are eight cervical, 12 thoracic, five lumbar, five sacral and one coccygeal spinal segments in humans. The number of these segments varies slightly in different species.2

Fine Organization of the Spinal Cord

The fine structure of the mammalian spinal cord was studied mainly on rodents, cats and primates. The most important results were those of Rexed2,3 and Scheibel and Scheibel4-6 on the cat spinal cord. Although the overall organization of the human spinal cord is similar to that of other mammals, there are some differences both in the cyto- and myeloarchitecture. In the past few years several studies made an effort to describe the structure of the human spinal cord and gave a detailed account of its features. Here we give a short description of the human spinal cord and where necessary refer to the important differences between human and other mammalian species (monkey, cat, rat and mice).

Cyto- and Dendroarchitecture

The laminar distribution of spinal neurons has been widely accepted. Its main advantage is its simple and comprehensive scheme of spinal cord organization and physiological properties can also be correlated to this structural arrangement.

Cytoarchitectural laminae are characterized by the density and topography of spinal neurons in the grey matter and can usually be identified on thick cross sections (fig. 1). In addition, each lamina has its own characteristics which are particularly distinct at the level of cervical and lumbar enlargements. Most of the information about dendritic territories has been obtained by using Golgi impregnation methods. In addition to the laminar arrangement in the coronal plain, in the ventral horn the cervical and lumbar motoneurons form rostrocaudal motor columns7 (fig. 1).

Figure 1. a) Cross section of the lumbar portion of the rat spinal cord showing the layered arrangement of the hemicord.

Figure 1

a) Cross section of the lumbar portion of the rat spinal cord showing the layered arrangement of the hemicord. The white matter is separated from the grey matter by a broken line. LSN= lateral spinal nucleus which takes place outside the grey matter in (more...)

Lamina I is the dorsalmost lamina which covers the tip of the dorsal horn. It has a loosely packed neuropil and a low neuronal density with neurons of variable size and distribution. The most typical neuron is the so-called Waldeyer8 cell: large, fusiform neuron with disk-shaped dendritic domain.9-12 However, in cat and rat also small and medium-sized pyramidal neurons were identified in this lamina3,10,11,13,14 and characterised as fusiform, pyramidal and multipolar cells.13

Lamina II appears as a darkly stained band in Nissl-stained sections due to its high neuronal density (substantia gelatinosa, Rolando, 1824). In cat and rodents the inner and outer zones can be distinguished2,3 although in humans there is not a clear separation between these zones. The neuronal population consists of small fusiform neurons. There are two main cell types which form the majority of the population of lamina II: the islet cells with a rostrocaudal axis and the stalked cells with a dorsoventral dendritic tree. Other types of neurons have been described such as arboreal, curly, border, vertical, filamentous and stellate cells.9,15-18 It is possible, however, that some of these latter neurons correspond to each other or to the two main cell types. Islet cells contain GABA therefore they are considered as the inhibitory cells of this lamina.

Lamina III can be easily distinguished from lamina II by its lower neuronal density and by the presence of intermediate size neurons. This layer has a mixed population of antenna-like and radial neurons.19-21 These cells have a simpler dendritic morphology than those in layer II.9,22,23 Many of the above cells contain inhibitory neurotransmitters: GABA or glycine.24

Lamina IV in man and cat has a variety of antenna-like cells and the so-called transverse cell.7,9,23 Most of their dendrites originate dorsally on the cell body and spread towards lamina II and III. In animals, the axons of lamina IV neurons mainly enter the spinocervical tract, which is vestigial in humans. Most probably human lamina IV neurons project to the spinothalamic tract.25 Laterally from this lamina there is a small group of neurons embedded in the lateral funiculus: the lateral spinal nucleus26 (fig. 1). Its neurons project to the midbrain and brainstem and send processes to lamina IV itself.

Lamina V-VI have a similar cyto- and dendroarchitecture. The medial part contains fusiform and triangular neurons. The lateral part is not clearly separated from the dorsolateral funiculus. This part corresponds to the reticular formation in the brainstem and consists of medium-sized multipolar neurons.

Lamina VII occupies the intermediate zone of the grey matter and is formed by an homogeneous population of medium-sized multipolar neurons. In the appropriate segments it contains some well-defined nuclei, such as the intermediolateral nucleus (T1-L1; medially) and the dorsal nucleus of Clarke (T1-L2; laterally). The intermediolateral nucleus plays a role in the autonomic sensory and motor functions and the axons of neurons from the dorsal nucleus of Clarke form the ascending fibres of the dorsal spinocerebellar tract.

Lamina VIII has, unlike laminae I-VII a dorsoventral extension. It contains a variety of neurons with dorsoventrally polarized dendritic tree. The largest multipolar neurons can be distinguished from motoneurons only by their finer Nissl bodies by using conventional morphological techniques.27

Lamina IX is made up of groups of cells that form motor nuclei. Motoneurons have a unique position in this lamina, being the only spinal cord neuron which has its axon almost entirely in the peripheral nervous system. The α-motoneurons have the largest somata in the cord (50 x 70 μm) whilst the γ-motoneurons are smaller. Motoneurons can be easily recognized by the abundance of Nissl bodies in their cytoplasm and their multipolar shape (fig. 1). Their dendrites extend for long distances, dorsally as far as lamina VI. Small neurons at the medial border of the motor nucleus are identified as the short-axoned inhibitory interneurons, the Renshaw cells. Although Rexed's classification2,3 did not differentiate between motoneuron groups in lamina IX, these neurons can be divided into four separate columns in the human cord: the ventromedial, ventrolateral, dorsolateral and central columns28 (fig. 2).

Figure 2. Schematic representation of the dendroarchitecture of spinal motoneurons in various motor columns.

Figure 2

Schematic representation of the dendroarchitecture of spinal motoneurons in various motor columns. The ventromedial motoneurons (IX-vm) form vertical and longitudinal dendritic branches (not shown), motoneurons in the ventrolateral (IX-vl) and central (more...)

Motoneurons projecting to the axial muscles are found in the ventromedial column,28,29 those innervating proximal musculature of the limbs occupy medial and ventral position while neurons innervating distal limb muscles are located in dorsal and lateral positions. In all but one (dorsolateral) motoneuron column the dendritic polarization is longitudinal and dendritic trees overlap for a long distance (fig. 2). Such a dendritic organization favours synchronization and synergy for axial, proximal and calf muscles.4,5 In contrast to these columns, motoneurons in the dorsolateral column have radially oriented dendritic trees without much overlap of their dendrites (fig.2). This dendritic arrangement favours precise contacts with segmental afferents and may contribute to a more precise control of movements of distal muscles.

Lamina X

This lamina corresponds to the substantia grisea centralis, the grey matter around the central canal. Two cell types can be recognized: (1) Bipolar cells with fan-shaped dendritic tree (dorsal portion of lamina X) and (2) bipolar cells with poorly ramified longitudinal dendrites (ventral portion).30

Interneurons in the Spinal Cord

Interneurons are probably the most important modulating cell types in the spinal cord. The importance of spinal interneuronal networks has only recently been acknowledged although the flexibility of these networks became apparent as early as in the 1950s.

Initially only electrophysiological approaches were used, later the precise location, morphology and immunohistochemical features helped to distinguish special interneuronal classes.

The very first morphologically and physiologically identified interneurons were the Renshaw cells and Ia interneurons (Renshaw cells project on motoneurons and thus establish the recurrent inhibition, whereas Ia interneurons are activated by Ia afferents of agonist muscles and inhibit antagonistic motoneurons).31,32 Renshaw cells, Ia and Ib inhibitory interneurons, interneurons in disynaptic and polysynaptic reflex pathways and interneurons mediating descending commands were the “classical interneurons” and their function was thoroughly analyzed in a series of studies. Recently a number of new interneurons modulating special functions were described, e.g.,interneurons involved in the clasp-knife reflex, bladder function, control of respiration and last-order premotor interneurons, etc. It is expected that the number of these highly specialized interneurons will further increase with time (for recent reviews and references see Jankowska 2001,33 Edgley 200134).

Most interneuron types have also been characterised by their neurochemical features. Renshaw cells, for example, express not only glycine, their characteristic inhibitory neurotransmitter, but they reportedly synthesize calcium binding proteins calbindin-D28k and parvalbumin.35-37

This short description of spinal interneurons suggests that the fine control of spinal functions mostly depends on the integrity of spinal interneuronal networks. It should be noted that interneurons named after their characteristic input (Ia, Renshaw, etc) receive a variety of multisensory inputs of different origins and these inputs together determine what the interneuron actually will do.

Glial Cells of the Spinal Cord

The central nervous system contains numerous nonneuronal, nonexcitable cells. The largest class of these cells is neuroglia or “nerve glue” a name taken from the Greek. The main glial cell types are astrocyte, oligodendrocyte, ependyma and microglia. Astrocytes together with oligodendrocytes and ependyma develop from the neuroectoderm whilst microglia is considered to be derived from blood monocytes.

Astrocytes are large cells with a stellate morphology. These very numerous fine processes radiate in all directions and contain a specific form of cytoskeletal intermediate filament, the glial fibrillary acidic protein (GFAP, fig. 3e). Astrocytes come in two main forms: fibrous astrocytes are primarily found in white matter and protoplasmic astrocytes in the grey matter. The latter subtype has long thin processes containing much less GFAP than the fibrous astrocytes, but can be characterized by the presence of glutamine synthase. Although these types of astrocytes differ anatomically, the developmental, functional and biochemical differences between them are not fully understood.38

Figure 3. a) Fluorescent photograph of oligodendrocytes present in the spinal cord visualized with carbonic anhydrase II immunostaining.

Figure 3

a) Fluorescent photograph of oligodendrocytes present in the spinal cord visualized with carbonic anhydrase II immunostaining. Scale bar = 50 μm. b) High magnification photograph shows two oligodendrocytes stained by using carbonic anhydrase enzyme (more...)

During embryonic development astrocytes guide the migration of neurons while in the mature CNS they form a structural scaffolding for other cells. Astrocytic foot processes form perivascular cuffs around CNS capillaries thus contributing to the formation of blood-brain barrier and similar processes protect the CNS from external influences at the pial surface (glial limitans externa). Apart form many other metabolic functions astrocytes are thought to transport ions and fluid from the extracellular space to vessels and they can release a number of factors which promote axonal growth.38 Astrocytes are able react to many deleterious effect to the CNS. Morphologically this process is characterized by the appearance and proliferation of so-called reactive astrocytes (fig.3). Although this astrocytic healing process is often called glial repair the proliferation of astrocytes can lead to the formation of glial scar which is considered as the impediment of axonal growth and regeneration in the CNS.

Oligodendrocytes produce myelin within the CNS. One oligodendrocyte is able to myelinate several adjacent axons (fig. 3b). The myelin is formed by these cells wrapping spiral layers of cell membrane around the axon. The inner surfaces of the cell membranes fuse and form the so-called major dense line. The myelin contains special lipids and proteins, for example the glycolipid galactocerebroside and the myelin basic protein (MBP, fig. 3c). The myelin in the CNS is the target of several serious diseases such as multiple sclerosis and leukodystrophies. Outside the CNS myelin is formed by Schwann cells which myelinate only a single axon. Schwann cells normally are not present in the CNS (fig. 3g) and in the case of the spinal cord and brainstem there is a distinct junction between the PNS- and CNS-type myelin called transitional zone and characterized by a complex glial structure.39

The CNS has its unique set of immune cells the brain macrophages. The most important and characteristic CNS macrophages are the microglial cells40 (fig. 3). The phenotype of microglia suggests that they are dendritic antigen-presenting cells41 expressing class II (I-A) major histocompatibility antigens. Under pathological circumstances microglial cells become activated, increase in size and number and are usually supplemented by blood-born monocytes.

Connections of the Spinal Cord with Other Parts of the CNS

The spinal cord has its own intrinsic pathways which are called propriospinal connections. The rest of the fibre tract system connects the spinal cord to other parts of the CNS and are described here as descending and ascending pathways. There are, of course, marked species differences, the most well known are those of the corticospinal system.

Intrinsic Pathways

These tracts not only establish connections between different neuronal groups and segments of the spinal cord but also act as relays between descending pathways and intrinsic spinal neurons. Accordingly, well defined ascending and descending white matter bundles are committed to propriospinal functions.

The Lissauer's tract tract can be localized between the entering dorsal roots and lamina I. It is mainly composed of unmyelinated descending and ascending fibres and both types extend a few segments. The majority of these fibres originate from the dorsal roots whilst the rest is intrinsic in nature terminating on marginal and substantia gelatinosa cells. The comma tract is a comma-shaped thin fibre bundle in between the fasciculi cuneatus and gracilis. It contains descending fibres from the cervical dorsal roots. The septomarginal tract is situated in the dorsal white matter and its position varies at the level of different segments. It consists of descending dorsal root and intrinsic fibres. The cornucommissural tract can be found along the dorsal commissure and contains ipsilaterally running descending and ascending propriospinal fibres. The anterior and lateral ground bundles are present throughout the spinal cord being most developed at the levels of enlargements. They contain both ascending and descending long and short fibres. They originate in the ipsilateral hemicord and terminate throughout the grey matter.

Ascending Pathways

The ascending pathways are formed by the central axons of dorsal root ganglion cells entering the spinal cord via the dorsal roots. They either enter an ascending fibre tract (dorsal column pathways) or terminate in the spinal grey matter. About two-third of these fibres are fine, unmyelinated, slowly-conducting C fibres. The myelinated fibre components can be classified as fast-conducting, large, myelinated Aβ, and slower-conducting, thinly myelinated Aδ fibres. Primary sensory fibres either terminate in the dorsal column nuclei of the medulla or in the superficial dorsal horn according to a segregated pattern. Thin fibres related to temperature and pain terminate in laminae I and II, whereas coarse fibres terminate in deeper layers (laminae III-V) and in the ventral horn as well (proprioceptive afferents). Furthermore, primary afferents coming from cutaneous receptors terminate almost exclusively in lamina II in rat and cat whilst visceral and muscle afferent terminals are mainly confined to laminae I and V.42,43

The dorsal column pathways include the medially located fasciculus gracilis (Goll) and the laterally situated fasciculus cuneatus (Burdach). The fasciculus gracilis contains dorsal root afferents from the lower limbs and lower part of the body, the fasciculus cuneatus from the upper limb and upper part of the trunk. The fibres synapse on neurones of the nucleus gracilis and nucleus cuneatus, respectively. These pathways play role in discriminative sensory tasks, such as two-point discrimination, detection of speed and direction of movements and judging of cutaneous pressure.44 The spinothalamic tract originates from neurons in laminae I,V,VII and VIII,25 however the distribution of spinothalamic neurons shows significant species differences. In humans the axons cross to the ventrolateral column and terminate in the ventral posterolateral and in the central lateral nuclei of the thalamus. In other mammals they terminate mainly in the posterior thalamic nuclear complex. Functionally, this tract conveys the accurate localization of pain and thermal stimuli. Ventrolateral cordotomies presented evidence that other tracts may also transmit pain stimuli.45 The spinoreticular tract originates from cells situated bilaterally throughout the spinal grey matter. The ascending fibres in the ventral and lateral funiculi terminate in several nuclei of the reticular formation. Many spinothalamic ascending fibres also give collaterals to reticular nuclei. This pathway is responsible for carrying a variety of sensory information. The spinocervicothalamic tract uses an intermediate nucleus in the spinal cord, the lateral cervical nucleus, which is consistent in lower mammals but often absent in human spinal cords. Afferent fibres to this nucleus arise from the ipsilateral lamina IV in all cord segments. Neurons from the lateral cervical nucleus project to the contralateral thalamus via the medial lemniscus. This system is involved in tactile conditioned reflexes, tactile and proprioceptive placing and size discrimination. The spinocerebellar tracts (dorsal and ventral) carry information primarily arising from the lower extremities. The dorsal spinocerebellar tract is formed by axons of the ipsilateral nucleus dorsalis of Clarke (present in Th1-L2 segments in humans) and projects to the vermis and the paravermal regions of the cerebellum. It conveys information from muscle spindles, Golgi tendon organs, joints and mechanoreceptors of the lower extremities. Axons of cells situated in laminae V and VII in the lumbosacral spinal cord form the ventral spinocerebellar tract. It projects to the vermis and paravermal region of the cerebellum and probably carries information about the interrelationship of different muscle groups. Equivalent information from the upper extremities are conveyed by the cuneocerebellar and the rostral spinocerebellar tracts of the spinal cord.

Descending Pathways

The corticospinal tract is most developed in higher primates and species differences are most pronounced for this tract. The cells of origin are located in the motor cortex and their axons form the pyramidal tract. In most mammals fibres from neurones in the postcentral gyrus also contribute to this tract. In humans the bulk of the fibres cross in the lower medulla and form the lateral corticospinal tract whereas uncrossed fibres remain in the ventral funiculus and then cross in the ventral commissure. In some species the organization of this tract is different.46,47 Functionally, the corticospinal pathway exerts a fine and amplified motor control by influencing other descending pathways.48,49 Fibres of the reticulospinal tracts originate from the dorsal and central parts of the medulla and the pontine tegmentum. The terminal distribution of medial reticulospinal fibres is very dense in the ventral horn of the enlargements while the lateral reticulospinal tract fibres terminate in laminae I and V.50 Fibres of the vestibulospinal tract originate from the lateral and medial vestibular nuclei. Both lateral and medial tract fibres terminate ipsilaterally in laminae VII and VII and form mono- or polysynaptic inhibitory connections with motoneurons, especially with those of neck and back muscles. The rubrospinal tract is well developed in lower mammals and less developed in humans. Its fibres originate from the caudal magnocellular part of the red nucleus and project according to a somatotopic pattern contralaterally to laminae V-VII. In cat there is a direct rubrospinal connection to motoneurons.51 The tract exerts excitatory effects on flexor motoneurons and inhibits extensor motoneurons. The tectospinal tract tract originates from the superior colliculus and terminates contralaterally in the ventral horn of the upper cervical cord where its fibres establish multisynaptic connections with motoneurons of neck muscles.

Apart from the major descending tract, there are many minor fibre bundles originating from the interstitial nucleus of Cajal, solitary and retroambiguous nuclei, and the paraventricular nucleus of the hypothalamus. Noradrenergic fibres descend from the locus coeruleus and the lateral pontine nuclei to the grey matter and to the intermediolateral nucleus, respectively. Serotonergic projections arise from the raphe magnus and raphe pallidus and obscurus nuclei terminate either in laminae I and V (raphe magnus fibres) or in the ventral horn (rest of the fibres).

Function of the Spinal Cord

The spinal cord is a highly organized and complex part of the central nervous system. Its complexity is due to the role it plays in the 3 most important functions of the individual: sensation, autonomic and motor control. If it was to simply report to the brain the information that it receives from the large number and variety of afferent inputs and relay back to the motoneurons and preganglionic neurons the outcome of processing performed by the supraspinal centres the situation would be more straight forward. However, as is well established, this is not the case and the spinal cord has, in addition to relaying information from the rest of the body to the brain and receiving efferent commands from varied portions of the brain the ability to integrate and modify both afferent signals from the periphery, and efferent signals from segmental afferents and supraspinal centres. Thus there is a complicated network of neurons that normally operates in conjunction with the rest of the CNS to allow perfect control of sensory, autonomic and motor functions. This complex circuitry is critically dependent on its connections with the brain and it can not function appropriately when it is either completely or even partially disconnected from it. It is rather regrettable, that we understand so little of the potential of the complex intrinsic circuitry of the spinal cord that when it looses connection with the brain we are unable to exploit its' potential function and restore deficits caused by spinal cord lesions.

In spite of the fact that the physiology of the spinal cord has been intensively investigated for at least a century it keeps revealing new surprising phenomena.

In this chapter only a brief account will be given of its main functions.

Sensory Processing

In an oversimplified manner it can be stated that the somatic afferent functions that are processed in the spinal cord constitute the following: (a) pain and temperature, (b) touch, and (c) proprioception. Different sense organs in the peripheral structures initiate these sensory modalities, but the processing of them is usually carried out by a network of neurons in the spinal cord that are common to several of these different modalities of sensation.

Pain and Temperature

The peripheral receptors for various modalities of sensation are specialised sense organs that are contacted by axons from dorsal root ganglion neurons. These neurons have a peripheral process and a central branch that enters the spinal cord where they branch. These neurons that are directly linked with the peripheral structures are called first order neurons, and their role in processing of sensory information is largely determined by their branching pattern. Figure 4a illustrates some of the sense organs of the first order neurons that are involved in pain and temperature sensation and also shows that the main target of the branches of the central portion of this first order neuron terminates and synapses on neurons in the substantia gelatinosa. It is from this part of the dorsal horn where the second order neurons give rise to their processes which convey the information to other parts of the spinal cord and brain. However, there are ascending and descending branches of the second order neurons that synapse on cells in different segments of the spinal cord and on more ventral interneurons that are concerned with control of movement and integration of somatic afferent inputs with those from other parts of the central nervous system.52 Thus these second order neurons play a crucial role in the processing of sensory information within the spinal cord. Not only somatic afferent fibres converge into the neurons in the substantia gelatinosa, but visceral sensation and pain also converges onto this group of second order neurons. In addition there is a strong input from various structures of the brain that impinge upon neurons in the substantia gelatinosa modify the input from the periphery and in this way the outcome of sensation (for further reading see Brown 1991,53 Schomburg 199054). It is partly because of this convergence of inputs to this part of the spinal cord that sensation is not simply the result of particular peripheral inputs.

Figure 4. a) and b) illustrates schematically the types of sensory nerve endings in peripheral tissues innervated by sensory nerves (peripheral processes).

Figure 4

a) and b) illustrates schematically the types of sensory nerve endings in peripheral tissues innervated by sensory nerves (peripheral processes). It also shows the central processes and their lamination in the spinal cord and medulla. The insert on the (more...)

Touch and Tactile Discrimination

The sensation of light touch is initiated from specialized sense organs in the skin or connective tissue or from free nerve endings in the dermis. The sense organs are contacted by axons from the cells of dorsal root ganglia and the information reaches the spinal cord via the central branch of the neurons of the dorsal root ganglion cells. These central branches form long tracts which give off branches to interneurons of the posterior horn in laminae VI and VII. The second order neurons within the spinal cord that process information about touch are thus in lamina VI and VII.

The same structures that are involved in the sensation of touch are also contributing to more sophisticated sensory functions such as two point discrimination, awareness of movement of body parts, as well as the position of various body parts in relation to each other. However these functions are also critically dependent on proprioception.

Proprioception

The sense organs that convey this modality of sensation are located in muscles, tendons and joints (Figs. 4b and 5). The structure of these is rather complex and indicate their important function in conveying the initial signal. In the muscle the annulospiral and flower spray endings of the spindles are monitoring muscle length and this task is complicated by the fact that the spindles are themselves a group of muscle fibres ensheathed in a connective tissue capsule and contacted by 2 types of sensory fibres. In addition to their sensory innervation the muscle fibres within the spindle receive their own motor innervation from small motoneurons and axons referred to as gamma efferents. Thus by relaxing or contracting the muscle fibres within the spindle the message about the state of the muscle is modified even before it reaches the spinal cord. In muscle tendons there are organs (Golgi tendon organs) which monitor the stretch imposed upon the tendon, and the Pacinian corpuscules within joints and close to bony structures monitor the pressure exerted upon these structures. The axons of sensory nerves that carry the information from the spindles towards the spinal cord are among the largest and fastest conducting nerves in the body. The central branch make up the medial division of the dorsal root as it enters the spinal cord. The central branch splits after entering the spinal cord and some of these enter the anterior horn where they synapse directly onto motoneurons to initiate a monosynaptic reflex, or onto interneurons to exert via interneurons more sophisticated control over locomotor activity.55 These monosynaptic connections are rather unique in that there is a high degree of specificity and muscle spindle afferents from a given muscle contact only motoneurons that innervate the muscle of the origin of this afferent input. Other branches enter the posterior funiculus and ascend towards Clarke's nucleus in the posterior grey horn. Some descending and ascending branches synapse on interneurons in laminae V, VI, and VII. Axons of these cells cross the midline and ascend in the ventral spinocerebellar tract to communicate with the cerebello-olivary system.

Figure 5. a) and b) The sensory and motor innervation of the mammalian muscle spindle is illustrated in a.

Figure 5

a) and b) The sensory and motor innervation of the mammalian muscle spindle is illustrated in a. This figure also shows the schematic picture of the cross section of the spinal cord with the various inputs to γ-motoneurons (left) and α-motoneurons (more...)

Thus the various parts of the sensory system inform the brain about the external and internal stimuli impinging onto the extremities and trunk. However this information undergoes considerable processing by the circuitry of the spinal cord and is continuously modified by it.54

Motor Control

Reflexes

Our understanding of spinal cord physiology has until recently been dominated by observations of Sherrington56 (1910) and his colleagues that the structures of the spinal cord are able to produce stereotyped responses to external stimuli. These responses were referred to as reflexes and carefully defined and observed. The simplest of these reflexes is the monosynaptic stretch reflex, elicited by activation of the IA afferent fibres that originate from the muscle spindle, and when activated produces contraction of the synonymous muscle. However even the study of this simple reflex revealed a great degree of complexity in the spinal cord circuitry. The strength of muscle contraction in response to the same stimulus was not always the same and was influenced by preceding activity of the spinal cord. In order to explain some of the findings associated with the variability of reflex activity it was necessary to consider events such as temporal and spatial summation of excitatory inputs, and inhibitory influences from other sources.Thus even the simplest “reflex” turned out to display considerable variability.56 Nevertheless the information about the behaviour of the structures that mediate the responses to various stimuli in the spinal cord obtained by the study of reflex activity was of immense importance. It taught us that the observation of temporal and spatial summation of excitatory inputs is caused by the ability of neurons to add up excitatory postsynaptic potentials (EPSPs) and therefore when 2 inputs, each of which is too weak to produce a response on its own, impinge upon a neuron simultaneously, or with a slight delay, they can produce a response since the depolarisation of the cell reaches a threshold level which fires off an action potential. These rules apply even in the case of the simplest reflex response such as the stretch reflex, which is monosynaptic and the integration is carried out by only one cell, the motoneuron. All other reflexes are polysynaptic, and therefore each neuron involved in the response can contribute to the final outcome i.e., the motor response to a particular stimulus (see fig. 5). The study of these relatively simple spinal reflexes revealed other features of the system, i.e., that neurons are not only excited, but can be inhibited by particular inputs. Such inhibition is either postsynaptic so that the membrane potential of the postsynaptic neuron increases and thus the same excitatory input fails to depolarize the neuron sufficiently to initiate an action potential, or inhibition can be presynaptic, by which the amount of excitatory transmitter released from the presynaptic terminal is reduced.

Patterned Movements Organised by the Circuitry of the Spinal Cord

In addition to the monosynaptic stretch reflex the circuitry of the spinal cord can generate patterned responses that involve movement of several joints. The best explored reflex of this type is the flexor, or withdrawal reflex in response to various sensory stimuli, and in particular in response to pain. During this reflex the extremity is withdrawn from the site of the stimulus. The flexor reflex is a complex movement which involves a highly organized sequence of activation and inhibition of motoneurons to particular muscles. It affects muscles of the contralateral limb so that the animal is supported during the time when the limb is involved in the flexor reflex and is lifted off the ground. Another patterned response that can be organized by the spinal cord is stepping. In acutely spinalised animals Brown57 (1911) showed that the spinal cord could trigger rhythmic walking movements. These movements are of interest, since they do not depend entirely on sensory inputs and are generated by neurons located in the spinal cord. The group of neurons responsible for the organisation of this movement has been referred to as central pattern generator (CPG).58

Most of the information on spinal cord CPGs in mammals has been obtained on experimental animals such as rats or cats. However, whether the spinal cord of primates and humans is able to produce the same responses when disconnected from the brain is less well documented. So far the available information suggests that the isolated spinal cord of primates or humans is unable to generate such primitive stepping movements as those described for the cat.59 Nevertheless some spinal reflex responses are preserved after complete spinal cord lesion in humans. These include the stretch reflex, which is often exaggerated and the flexor reflex. However, these responses are not stereotyped and change when they are elicited repetitively.60 Thus even the human spinal cord is able to generate complex responses, which are influenced by repeated activity, by mechanisms that we do not understand.

The localisation of supraspinal locomotor regions is well established in the sense that electrical stimulation of such regions can elicit walking, or even galloping in decorticate cats suspended above a treadmill belt.61 Stimulation of these areas in primates prepared in a similar manner as cats, also elicited walking and trotting. However the monkeys walked on all 4 limbs.62 Thus like in cats the mesencephalic locomotor centre was able to activate the locomotor function of the primate spinal cord, but without the connection with this centre the stimuli that induced locomotor activity in the spinal cat were unable to do so in the spinal monkey.

Until now this section described the potential of the spinal cord to produce integrated responses without depending on the influences from the brain. However it is important to emphasize that this situation is rare and even after spinal cord injury in man the separation of the spinal cord from the brain is rarely complete. It is therefore important to consider spinal cord function in relation to the control systems that normally regulate its performance. Figure 6 summarizes the various influences from the higher centres that may influence the performance of the spinal cord circuitry.

Figure 6. The scheme illustrates the various structures involved in the control of locomotor function.

Figure 6

The scheme illustrates the various structures involved in the control of locomotor function.

Since this book is concerned with the possibility that neuronal or glial transplants will either replace damaged parts of the spinal cord, or encourage existing structure to regenerate or resume their function it seems pertinent to mention observations that concern the importance of various descending pathways for recovery of locomotor activity. It appears that in patients with spinal cord injuries the preservation of the ventral funiculi is best correlated with recovery of gait,63 while patients with well preserved sensation of touch and position, but severe damage to the anterior part of the cord have a poor chance to regain the ability to walk.59 In monkeys trained to walk on a treadmill return of locomotor performance after spinal cord injury was critically dependent on the preservation of at least one ventrolateral funiculus. Retrograde labelling of the preserved funiculus showed that the axons in the preserved funiculus originates in the vestibular, reticular and raphe nuclei.62 Thus it appears that these structures are of critical importance for the control of the spinal cord central pattern generator. In the context of the topic discussed in this book this finding is of utmost importance, for it indicates that for successful restoration of motor function efforts should be made to reconnect particular structures, rather then haphazardly investigate indiscriminate growth of axons that may not be able to contribute to improvement of function.

Autonomic Function

There are important structures within the mammalian spinal cord that regulate various autonomic functions of the body and can be severely affected when the spinal cord is disconnected from the brain. Generally the autonomic nervous system is divided into sympathetic and parasympathetic components. The cells that control these two separate divisions occupy a typical position within the spinal cord of mammals. This is illustrated in Figure 7. The figure shows that the preganglionic neurons of the sympathetic system are localised in the thoracic and lumbar part of the spinal cord, while neurons that control the parasympathetic ganglia originate in the sacral region.

Figure 7. The figure illustrates the location of the sympathetic neurons in the spinal cord and the targets they innervate.

Figure 7

The figure illustrates the location of the sympathetic neurons in the spinal cord and the targets they innervate. Modified from ref. , Pansky and Allen, 1980, Review of Neuroscience.

These cells that regulate important autonomic functions are closely controlled and integrated by segmental afferent inputs, and by supraspinal inputs. Following disruption of these the autonomic control of functions such as bladder control, or control of defecation as well as sexual arousal can be seriously altered and it is an important consideration that these bodily functions be restored. Much of the information on the control mechanisms exerted by the spinal cord centres over these functions is concerned with those involved in micturition. The central pathways controlling lower urinary tract function are organized as simple on-off switch circuits summarized in Figure 8. The main control is concerned with the switch from the storage of urine mode to the micturition mode.

Figure 8. a) The location of the sympathetic and parasympathetic neurons in the lumbosacral cord, and the targets they innervate is shown.

Figure 8

a) The location of the sympathetic and parasympathetic neurons in the lumbosacral cord, and the targets they innervate is shown. Modified from ref. , Pansky and Allen, 1980, Review of Neuroscience. b) Illustrates a scheme that could explain the control (more...)

This switching is normally accomplished by supraspinal structures, but after spinal cord injury involuntary reflex voiding can be achieved (for details see de Groat et al, 199364).

Regarding other autonomic functions the information is less complete and beyond the scope of this brief summary of spinal cord physiology.

Neurotransmitters and Receptors in the Spinal Cord

The communication between the neurons of the central and peripheral nervous system and between neurons and their nonneuronal targets is established by using a variety of chemical messengers, the neurotransmitters. There are other molecules, the so-called neuromodulators which coexist with the neurotransmitters and probably regulate their function. All these molecules are different in their chemical nature as they belong to the families of amino acids, monoamines, peptides, opiates etc. The mapping of neurotransmitters involves the histochemical localization of synthesizing and degradating enzymes of the transmitter as well as recent methods, such as immunocytochemistry, receptor autoradiography, in situ hybridization, the stimulated cobalt uptake method65 and topobiochemistry. All these recent investigations led to the better understanding of spinal mechanisms of outstanding importance, for example spinal motor functions and pain. However, it should be noted that remarkably more information is available on the mechanisms of neurotransmission in the dorsal horn and intermediate grey matter than in the ventral horn. This short overview is not intended to provide a detailed account of neurotransmitters and receptors in the spinal cord. Therefore for more information on these systems see recent reviews including those by Todd and Spike 1993,66 Coggeshall and Carlton 199767 and Budai 2000.68

Acetylcholine

Cholinergic neurotransmission plays an outstanding role in the function of the spinal cord and therefore has been extensively studied. Although acetylcholine (Ach) was the first neurotransmitter discovered in the PNS its localization in the CNS is far not as simple as it was thought in the early 1960s. It is relatively easy to detect histochemically acetylcholinesterase, the degradative enzyme for acetylcholine but it is present in both cholinergic and cholinoceptive neurons, the latter only receiving cholinergic innervation. Cholinacetyltransferase, the enzyme synthesizing acetylcholine, is more specific for cholinergic neurons. Histochemically detected acetylcholinesterase levels as well as enzymatic levels of cholinacetyltransferase are highest in laminae I and III,69,70 motor columns and in autonomic nuclei.70 Nicotinic acetylcholine receptors are preferentially found in dorsal horn laminae III and IV.71 A significant number of dorsal horn muscarinic and nicotinic receptors are thought to be located on the primary afferent terminals.71 Muscarinic acetylcholine receptors (M1 and M2) are most abundant in laminae II and IX72 and this fact suggests the presence of cholinergic inputs on motoneurons. Indeed, acetylcholinesterase- and cholinacetyltransferase-positive terminals were found on motor nerve cells and on Renshaw cells.73 This important cholinergic input arises from recurrent axon collaterals from adjacent motoneurons as well as supra- and propriospinal fibres. Renshaw cells receive cholinergic afferents from motoneuron axon collaterals, though they possess nicotinic cholinergic receptors (for review see refs. 69, 73, 74)

In addition to the well-established roles of Ach in spinal motor performance, both muscarinic and nicotinic receptors are thought to mediate antinociceptive effects.75

Monoamines

The spinal cord receives an abundant monoaminergic innervation from the brainstem nuclei. Noradrenergic fibres descend from the lateral tegmentum and locus coeruleus and subcoeruleus to the dorsal and ventral horn. Serotonergic (5-HT) fibres innervate the dorsal horn (from nucl. raphe magnus) and the intermediate grey matter and ventral horn (from nucl. raphe obscurus and pallidus), whereas dopaminergic fibres from the A11 cell group of the diencephalon invade the dorsal horn (for review see: Lindvall and Björklund 198376). 5-HT may be colocalized with substance P, CGRP, enkephalins and somatostatin in the raphe nuclei and their terminals.

Seven distinct 5-HT receptor subtypes have been identified (5-HT1-7), 3 of which (5-HT1-3) are associated with dorsal horn somatosensory processing. The activation of 5-HT receptors produce multiple physiological events as 5-HT receptors families either activate or inhibit second messenger systems.67,68

Dopamine D2 receptors are mainly found in dorsal horn laminae II-III. Accordingly, focal stimulation of the A11 cell group results in selective suppression of nociceptive responses originating from multireceptive rat spinal cord neurons.77

There is more noradrenalin than dopamine in the spinal cord. This abundance of noradrenergic innervation is accompanied by a dense concentration of α2-adrenergic receptors in the dorsal horn.67,68 The clinical significance of noradrenergic neurotransmission is indicated by the finding that activation of α2-adrenergic receptors in the dorsal horn induces analgesia in humans and experimental animals.

Amino Acids

Excitatory amino acids (EAAs), such as aspartate and glutamate are released by some interneurons (aspartate), Ia afferents and corticospinal fibres (glutamate).78 EAAs induce their excitatory actions via two broad categories of receptors: ionotropic and metabotropic glutamate receptors. Ionotropic receptors directly regulate the opening of ion channels and three subtypes of have been distinguished: NMDA, AMPA and kainic acid (KA) receptors. Metabotropic glutamate receptors are coupled to the G-protein and their action increases the turnover of polyphosphoinositides and induces the release of intracellular Ca++. EAA receptors have a relatively widespread distribution in the CNS, although some distinguished cell types display high density of certain specific receptors. Glycinergic neurons are mainly concentrated in the ventral horn: Renshaw cells and Ia interneurons are thought to use this inhibitory neurotransmitter. 79 Glycine receptors are either strychnine-sensitive or -insensitive ones. The activated strychnine-insensitive receptor is colocalized with the NMDA receptor complex and it plays a major role in the regulation of NMDA-mediated synaptic events. GABA (γ-amino butyric acid) is abundant throughout the spinal cord and GABA- as well as its synthesizing enzyme, glutamic acid decarboxylase-immunoreactive neurons are present in the ventral horn and lamina II.80-82 GABAA and GABAB receptor subtypes have been localized on primary afferent terminals and therefore GABA is thought to participate in the presynaptic modulation of nociceptive primary afferent inputs.

Neuropeptides

A wide variety of neuropeptides is present throughout the spinal cord. The list of peptides includes somatostatin, substance P, enkephalins, calcitonin gene-related peptide (CGRP), neuropeptide Y, oxytocin, opioid peptides, nociceptin, nocistation and some others. Most of the immunoreactivity is due to fibres entering the dorsal horn of the spinal cord but also numerous various cell types contain neuropeptides.66-68,83,84 The peptidergic immunoreactivity in dorsal horn fibres is only in part due to descending fibres from brainstem neurons, whereas many somatostatin and CGRP reactive fibres enter the dorsal horn via the dorsal root ganglia. The most intense immunoreactivity is always confined to the dorsal horn laminae where they probably play an important role in modulation of nociception.85 Functionally, CGRP expressed by motoneurons may have a trophic action on skeletal muscle cholinergic receptors86 but its role is obscured by the finding that some, but not all motoneurons contain this peptide. CGRP was found in most of the α-motoneurons innervating fast muscles while less motoneurons supplying slow muscles contained CGRP. In contrast, γ-motoneurons were only weakly stained for CGRP or totally devoid of CGRP labelling.87

References

1.
Weibl H. Zur Topographie der Medulla spinalis der Albinoratte (Rattus Norvegicus) Adv Anat Embryol Cell Biol. 1973;47:6.
2.
Rexed B. A cytoarchitectonic atlas of the spinal cord in the cat. J Comp Neurol. 1954;100:297–379. [PubMed: 13163236]
3.
Rexed B. The cytoarchitectonic organization of the spinal cord in the cat. J Comp Neurol. 1952;96:415–495. [PubMed: 14946260]
4.
Scheibel ME, Scheibel AB. Terminal axonal patterns in cat spinal cord. Ist ed. The lateral corticospinal tract Brain Res. 1966a;2:333–350. [PubMed: 4165493]
5.
Scheibel ME, Scheibel AB. Spinal motoneurons, interneurons and Renshaw cells. A Golgi study Arch Ital Biol. 1966b;104:328–353.
6.
Scheibel ME, Scheibel AB. Terminal axonal patterns in cat spinal cord. II. The dorsal horn. Brain Res. 1968;9:32–58. [PubMed: 5699822]
7.
Brown AG. Organization in the spinal cord. The anatomy and physiology of identified neurons New York: Springer. 1981
8.
Waldeyer H. Das Gorilla Rückenmark. Abh K Akad. Berlin: Wiss. 1888:1–147.
9.
Schoenen J. The dendritic organization of the human spinal cord: The dorsal horn. Neuroscience. 1982a;7:2057–2087. [PubMed: 7145088]
10.
Coimbra A, Lima D. Projections and neurochemical specificity of the different morphological types of marginal cellsIn: Cervero F, Bennett GJ, Headley PM, eds.Processing of Sensory Information in the Superficial Dorsal Horn of the Spinal CordNew York and London: Plenum Press,1988199–215.
11.
Lima D, Coimbra A. Morphological types of spinomesencephalic neurons in the marginal zone (lamina I) of the rat spinal cord, as shown after retrograde labelling with cholera toxin subunit B. J Comp Neurol. 1989;279:327–339. [PubMed: 2913071]
12.
Lenhossék MV. Der feinere Bau des Nervensystems in Lichte neuester Forschungen. Eine allgemeine Betrachtung der Strukturprinzipien des Nervensystems, nebst einer Darstellung des feineren Baues des Rückenmarkes. Berlin: Kornfeld. 1895:VII–409.
13.
Lima D, Coimbra A. A Golgi study of the neuronal population of the marginal zone (lamina I) of the rat spinal cord. J Comp Neurol. 1986;244:53–71. [PubMed: 3950090]
14.
Réthelyi M, Light AR, Perl ER. Synaptic ultrastructure of functionally and morphologically characterized neurons of the superficial spinal dorsal horn of the cat. J Neuroscience. 1989;9:1846–1863. [PubMed: 2723753]
15.
Bennett GJ, Abdelmoumene M, Hayashi et al. Physiology and morphology of substantia gelatinosa neurons intracellularly stained with horseradish peroxidase. J Comp Neurol. 1980;194:809–827. [PubMed: 6162863]
16.
Bennett GJ, Abdelmoumene M, Hayashi et al. Spinal cord layer I neurons with axon collaterals that generate local arbors. Brain Res. 1981;209:421–426. [PubMed: 7225801]
17.
Beal JA, Nandi KN, Knight DS. Characterization of long ascending tract projection neurons and nontract neurons in the superficial dorsal hornIn: Cervero F, Bennett GJ, Headley PM, eds.Processing of Sensory Information in the Superficial Dorsal Horn of the Spinal CordNew York and London: Plenum Press,1988a181–197.
18.
Todd AJ, Lewis SG. The morphology of Golgi-stained neurons in lamina II of the rat spinal cord. J Anat. 1986;149:113–119. [PMC free article: PMC1261638] [PubMed: 2447052]
19.
Maxwell DJ, Fyffe RE, Réthelyi M. Morphological properties of physiologically characterized lamina III neurones in the cat spinal cord. Neuroscience. 1983;10:1–22. [PubMed: 6646416]
20.
Maxwell DJ. Combined light and electron microscopy of Golgi-labelled neurons in lamina III of the feline spinal cord. J Anat. 1985;141:155–169. [PMC free article: PMC1166397] [PubMed: 4077713]
21.
Beal JA, Russell CT, Knight DS. Morphological and developmental characterization of local-circuit neurons in lamina III of the rat spinal cord. Neurosci Lett. 1988b;86:1–5. [PubMed: 2452390]
22.
Mannen H, Sugiura Y. Reconstruction of neurons of dorsal horn proper using Golgi-stained serial sections. J Comp Neurol. 1976;168:303–312. [PubMed: 956461]
23.
Réthelyi M, Szentágothai J. Distribution and connections of afferent fibres in the spinal cordIn: Iggo A, ed.Handbook of Sensory PhysiologyVol. II. Berlin: Springer,1973207–252.
24.
Todd AJ, Sullivan AC. Light microscope study of the coexistence of GABA-like and glycin-like immunoreactivity in the spinal cord of the rat. J Comp Neurol. 1990;296:496–505. [PubMed: 2358549]
25.
Smith MC. Retrograde cell changes in human spinal cord after anterolateral cordotomies. Location and identification after different period of survival Adv Pain Res Ther. 1976;1:91–98.
26.
Gwyn DG, Waldron HA. A nucleus in the dorsal lateral funiculus of the spinal cord of the rat. Brain Res. 1968;10:342–351. [PubMed: 4176805]
27.
Schoenen J, Faull RLM. Spinal cord: Cytoarchitectural, dendroarchitectural and myeloarchiotectural organizationIn: Paxinos G, ed.The Human Nervous SystemSan Diego: Academic Press,199019–53.
28.
Romanes GJ. The motor columns of the spinal cord. Prog Brain Res. 1964;11:93–116. [PubMed: 14300484]
29.
Schoenen J. Dendritic organization of the human spinal cord: The motoneurons. J Comp Neurol. 1982b;211:226–247. [PubMed: 7174892]
30.
Honda C, Lee C. Immunohistochemistry of synaptic input and functional characterization of neurons near the spinal central canal. Brain Res. 1985;343:120–128. [PubMed: 2412642]
31.
Jankowska E, Lindström S. Morphological identification of Renshaw cells. Acta Physiol Scand. 1971;81:428–430. [PubMed: 4101374]
32.
Jankowska E, Lindström S. Morphology of interneurones mediating Ia reciprocal inhibition of motoneurones in the spinal cord of the cat. J Physiol. 1972;226:805–823. [PMC free article: PMC1331178] [PubMed: 4118049]
33.
Jankowska E. Spinal interneuronal systems: Identification, multifunctional character and reconfigurations in mammals. J Physiol. 2001;533:31–40. [PMC free article: PMC2278593] [PubMed: 11351010]
34.
Edgley SA. Organisation of spinal interneurone populations. J Phys. 2001;533:51–56. [PMC free article: PMC2278602] [PubMed: 11351012]
35.
Antal M, Freund TF, Polgár E. Calcium-binding proteins, parvalbumin- and calbindin-D 28k-immunoreactive neurons in the rat spinal cord and dorsal root ganglia: A light and electron microscopic study. J Comp Neurol. 1990;295:467–484. [PubMed: 2351764]
36.
Carr PA, Alvarez J, Leman EA. et al. Calbindin-D28k expression in immunohistochemically identified Renshaw cells. Neuroreport. 1998;9:2657–2671. [PubMed: 9721951]
37.
Clowry GJ, Arnott GA, Clement-Jones M. et al. Changing pattern of expression of parvalbumin immunoreactivity during human fetal spinal cord development. J Comp Neurol. 2000;423:727–735. [PubMed: 10880999]
38.
Kimelberg HK, Norenberg MD. Astrocytes. Sci Amer April. 1989:44–52.
39.
Fraher JP. The CNS-PNS transitional zone of the rat. Morphometric studies at cranial and spinal levels. Prog Neurobiol. 1992;38:261–316. [PubMed: 1546164]
40.
Jordan FL, Thomas WE. Brain macrophages: Questions of origin and interrelationship. Brain Res Rev. 1988;13:165–178. [PubMed: 3289689]
41.
Klinkert WEF. Lymphoid dendrite accessory cells of the rat. Immunol Rev. 1990;117:103–120. [PubMed: 2258188]
42.
Cervero F. Dorsal horn neurons and their sensory inputsIn: Yaksh TL, ed.Spinal Afferent ProcessingNew York: Plenum Press,1986197–216.
43.
Molander C, Grant G. Spinal cord projections from hindlimb muscle nerves in the rat studied by transganglionic transport of horseradish peroxidase, wheat germ agglutinin conjugated horseradish peroxidase, or horseradish peroxidase with dimethylsulfoxide. J Comp Neurol. 1987;260:246–255. [PubMed: 3038969]
44.
Giuffrida R, Rustioni A. Dorsal root ganglion neurons projecting to the dorsal column nuclei of rats. J Comp Neurol. 1992;316:206–220. [PubMed: 1374085]
45.
Willis WD, Coggeshall RE. 1978 . Sensory Mechanisms of the Spinal Cord. New York: Plenum Press.
46.
Molander C, Grant G. The cytoarchitectonic organization of the spinal cord in the rat. Ist ed. The lower thoracic and lumbosacral cord. J Comp Neurol. 1984;230:133–141. [PubMed: 6512014]
47.
Schoen JH. Comparative aspects of the descending fiber systems in the spinal cord. Prog Brain Res. 1964;11:203–222. [PubMed: 14300479]
48.
Kuypers HGJM. The descending pathways to the spinal cord, their anatomy and function. Prog Brain Res. 1964;11:178–200. [PubMed: 14300477]
49.
Proudlock F, Spike RC, Todd AJ. Immunocytochemical study of somatostatin, neurotensin, GABA and glycine in the rat spinal cord. J Comp Neurol. 1993;327:289–297. [PubMed: 7678841]
50.
Holstege G, Kuypers HGJM. The anatomy of brainstem pathways to the spinal cord in the cat. A labelled amino acid tracing study. Prog Brain Res. 1982;57:145–175. [PubMed: 7156396]
51.
Holstege G. Anatomical evidence for an ipsilateral rubrospinal pathway and for direct rubrospinal projections of motoneurons in the cat. Neurosci Lett. 1987;74:269–274. [PubMed: 3561881]
52.
Jankowska E, Lundberg A. Interneurones in the spinal cord. Trends Neurosci. 1981;4:230–233.
53.
Brown AG. Nerve cells and nervous systems. Springer Verlag. 1991
54.
Schomburg ED. Spinal sensorimotor systems and their supraspinal control. Neurosci Res. 1990;7:265–340. [PubMed: 2156196]
55.
Jankowska E. Intraneuronal organisation in reflex pathways from proprioceptorsIn: Garlik DG, Kormer PJ, eds.Frontiers in Physiol Res Australia AC of Science 1984228–237.
56.
Sherrington CS. Flexion reflex of the limbs, crossed extension reflex and reflex stepping and standing. J Physiol. 1910;40:28–121. [PMC free article: PMC1533734] [PubMed: 16993027]
57.
Brown TG. The intrinsic factors in the act of progression in the mammal. Proc Roy Soc London. 1911;84:308–319.
58.
Grillner S. Locomotion in vertebrates. Central mechanisms and reflex interaction. Physiol Rev. 1975;55:247–304. [PubMed: 1144530]
59.
Eidelberg E. Consequences of spinal cord lesions repair motor function, with special reference to locomotor activity. Prog in Neurobiol. 1981;17:185–202. [PubMed: 6798636]
60.
Dimitrijevic MR, Nathan PW. Studies of spasticity in man. 6. Habituation, dishabituation and sensitisation of tendon reflexes in spinal man. Brain. 1973;96:337–354. [PubMed: 4715188]
61.
Shik ML, Orlovski GN. Neurophysiology of locomotor automatism. Physiol Rev. 1976;56:465–501. [PubMed: 778867]
62.
Eidelberg E. Locomotor control in monkeysIn: Eccles J, Dimitrijevic MR, eds.Upper Motoneuron Functions and DysfunctionsKarger,1985179–184.
63.
Nathan PW, Smith MC. Effects of two unilateral cordotomies on the motility of the lower limbs. Brain. 1973;96:471–494. [PubMed: 4517841]
64.
de GroatWC, Booth AM, Yoshimura N. Neurophysiology of micturition and its modification in animal models of human diseaseIn: Maggi CA, ed.Nervous Control of the Urogenital SystemPart of series: Burnstock G, ed. The Autonomic Nervous System. Harwood Ac1993227–290.
65.
Pruss RM, Akeson RL, Racke MM. et al. Agonist-activated cobalt uptake identifies divalent cation permeable kainate receptors on neurons and glial cells. Neuron. 1991;7:509–518. [PubMed: 1716930]
66.
Todd AJ, Spike RC. The localization classical transmitters and neuropeptides within neurons in laminae I-III of the mammalian spinal dorsal horn. Prog Neurobiol. 1993;41:609–645. [PubMed: 7904359]
67.
Coggeshall RE, Carlton SM. Receptor localization in the mammalian dorsal horn and primary afferent neurons. Brain Res Rev. 1997;24:28–66. [PubMed: 9233541]
68.
Budai D. Neurotransmitters and receptors in the dorsal horn of the spinal cord. Acta Biol Szeged. 2000;44:21–38.
69.
Kása P. The cholinergic systems in brain and spinal cord. Prog Neurobiol. 1986;26:211–272. [PubMed: 3523620]
70.
Aquilonius JM, Eckernas SA, Gillberg PG. Topographical localization of choline acetyltransferase within the human spinal cord and a comparison with some other species. Brain Res. 1981;211:329–340. [PubMed: 7237127]
71.
Gillberg PG, Wiksten B. Effects of spinal cord lesions and rhizotomies on cholinergic and opiate receptor binding sites in rat spinal cord. Acta Physiol Scand. 1986;126:575–582. [PubMed: 3012950]
72.
Scatton B, Dubois A, Favoy-Agid F. et al. Autoradiographic localization of muscarinic cholinergic receptors at various segmental levels of the human spinal cord. Neurosci Lett. 1984;49:239–245. [PubMed: 6493605]
73.
Woolf NJ. Cholinergic systems in mammalian brain and spinal cord. Prog Neurobiol. 1991;37:475–524. [PubMed: 1763188]
74.
Krnjevic K. Transmitters in motor systems. In: Handbook of Physiology. Washington DC: Am Physiol Soc. 1979:107–154.
75.
Pan HL, Chen SR, Eisenach JC. Intrathecal clonidine alleviates allodynia in neuropathic rats: Interaction with spinal muscarinic and nicotinic receptors. Anesthesiol. 1999;90:509–514. [PubMed: 9952159]
76.
Lindvall O, Björklund A. Dopamine- and norepinephrine-containing neuron systems: Their anatomy in the rat brainIn: Emson PC, ed.Chemical NeuroanatomyNew York: Raven Press,1983229–256.
77.
Fleetwood-Walker SM, Hope PJ, Mitchell R. Antinociceptive actions of descending dopaminergic tracts on cat and rat dorsal horn somatosensory neurones. J Physiol. 1988;399:335–348. [PMC free article: PMC1191668] [PubMed: 2841456]
78.
Urbán L, Thompson SW, Dray A. Modulation of spinal excitability: Cooperation between neurokinin and excitatory amino acid neurotransmitters. Trends Neurosci. 1994;17:432–438. [PubMed: 7530882]
79.
van den Pol AN, Görcs T. Glycine and glycine receptor immunoreactivity in brain and spinal cord. J Neurosci. 1988;8:472–492. [PubMed: 2892900]
80.
Magoul R, Onteniente B, Geffard M. et al. Anatomical distribution and ultrastructural organization of the GABAergic system in the rat spinal cord. An immunocytochemical study using anti-GABA antibodies. Neuroscience. 1987;20:1001–1009. [PubMed: 3299134]
81.
McLaughlin BJ, Barber B, Saito K. et al. Immunocytochemical localization of glutamate decarboxylase in rat spinal cord. J Comp Neurol. 1975;164:305–322. [PubMed: 1184786]
82.
Todd AJ, McKenzie J. GABA-immunoreactive neurones in the dorsal horn of the rat spinal cord. Neuroscience. 1989;31:799–806. [PubMed: 2594201]
83.
Seybold VS, Elde RP. Immunohistochemical study of peptidergic neurons in the dorsal horn of the spinal cord. J Histochem Cytochem. 1980;28:367–370. [PubMed: 6154731]
84.
Schoenen J, Lotstra F, Vierendeels G. et al. Substance P, enkephalins, somatostatin, cholecystokinin, oxytocin and vasopressin in human spinal cord. Neurology. 1986;35:881–890. [PubMed: 2582309]
85.
Yu LC, Zheng EM, Lundeberg T. Calcitonin gene-related peptide 8-37 inhibits the evoked discharge frequency of wide dynamic range neurons in the dorsal horn of the spinal cord in rats. Regul Pept. 1999;83:21–24. [PubMed: 10498340]
86.
Fontaine B, Klarsfeld A, Hökfelt T. et al. Calcitonin gene-related peptide, a peptide present in spinal cord motoneurons, increases the number of acetylcholine receptors in primary cultures of chick embryo myotubes. Neurosci Lett. 1986;71:59–65. [PubMed: 3491345]
87.
Piehl F, Arvidsson U, Hökfelt T. et al. Calcitonin gene-related peptide-like immunoreactivity in motoneuron pools innervating different hind limb muscles in the rat. Exp Brain Res. 1993;96:291–303. [PubMed: 7505750]
88.
Pansky B, Allen DJ. Review of NeuroscienceNew York: MacMillan Publishing Co. Inc.,1980.
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