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The existence of input plasticity in the deep cerebellar nuclear (DCN) cells of the adult cerebellum could have profound implications for our understanding of cerebellar function. Whereas the existence of plastic changes in mossy fiber (mf) synaptic responses in DCN neurons has been demonstrated in juvenile slices, there has so far been no direct demonstration of this form of plasticity in the adult cerebellum in vivo. In the present paper, we recorded from neurons in the anterior interposed nucleus (AIN) and stimulated the spinocerebellar tracts (SCT) directly or via the skin to obtain mf activation and the inferior olive to activate climbing fibers (cfs) in the nonanesthetized, adult, decerebrated cat. We used three different types of protocols that theoretically could be expected to induce plasticity, each of which involved episodically intense afferent activation lasting for 10 min. These were conjunctive mf-cf activation, which effectively induces plasticity in cortical neurons; mf and cf activation in a pattern resembling the protocol for inducing classical conditioning; and conjunctive activation of two excitatory mf inputs. None of these protocols had any statistically significant effect on the evoked responses in the AIN neurons. We conclude that the input plasticity for excitatory mfs in the AIN cells of the adult cerebellum in vivo is likely to be less effective than that of parallel fiber synaptic inputs in cerebellar cortical cells, at least in the timespan of 1 h.

Some cases of spinal cord compression syndrome at the cervical osteochondrosis are difficult enough to distinguisch from the other diseases.Case I: Muscle atrophy of the left hand is remarkable, but none of subjective and objective symptome in the right hand.Case II: Only muscle atrophy of the right schoulder is noted, but none symptome of the both lower extrimities.Case III and IV: ataxic gait is remarkable with sensory disturbance.Case V: ataxic gait is remarkable without sensory disturbance.We supposed that Case I and II were caused by lesion of the one side anterior column, and that case III and IV were caused by lesion of the bilateral posterior column chiefly rather than lateral corticospinal tract, and that case V by bilateral spinocerebellar tract.

Spinocerebellar tract (SCT) neurons projecting to lobules I and II of the cerebellar anterior lobe were identified by the retrograde horseradish peroxidase technique in the cat. Instead of a conventional stereotaxic approach, we removed ventral parts of the vermis of the posterior lobe and approached the posterior aspect of lobule I through the fourth ventricle. Under direct visual guidance, discrete injections were made into lobule I or lobule II with a glass micropipette. Neurons projecting to lobule I were located mainly in the central cervical nucleus (CCN), the medial part of lamina VII of L6 to the caudal segments, and in lamina VIII of S2 to the caudal segments (with crossed ascending axons). The latter two groups correspond to the medial lamina VII group of the lumbar to the caudal segments and the ventral horn group of the sacral-caudal segments of our previous studies. A small number of Clarke column neurons (with uncrossed ascending axons) also projected to lobule I. All of these neuronal groups projected to lobule II. In addition, large neurons in lamina V and in the border between laminae IV and V from S2 to the caudal segments projected to sublobule IIA, and more numerously to sublobule IIB (with crossed ascending axons). They belong to the dorsal horn group of the sacral-caudal segments of our previous studies. Spinal border cells (with crossed ascending axons) projected to sublobule IIB, and a small number, to sublobule IIA. It was suggested that the CCN neurons project more densely to the median region whereas Clarke column neurons project to the lateral part of these lobules.

There are a large number of ascending pathways, all of which have important direct projections to areas of the brain concerned with movement. In this chapter, a short summary of the types of sensory fibre which contribute to each tract, and the cells of origin of the tracts, will be given. The data is mostly from anatomical studies in the cat (and monkey); comparable human studies have not yet been performed.

Publisher Summary This chapter investigates the cerebellar projection areas and the input to the spinocerebellar tract (SCT) originating from the central cervical nucleus (CCN) by electrophysiologically in the cat. The CCN-spinocerebellar tract has now been identified as (1) receiving synaptic inputs from both the neck and the labyrinths, and (2) projecting to the vermis of the anterior lobe and to the posterior lobe. Experiments indicate that the input from the neck to CCN-SCT cells is primarily of joint origin probably from the same afferents which initiate tonic neck reflexes, influence extraocular motoneurones, and project to the flocculus. Wilson et al. have shown that the joint afferent impulses are relayed by neurones of Brodal and Pompeiano's group x; the latter neurones do not receive input from the labyrinth in contrast with the CCN cells, the majority of which are co-excited by impulses from both the neck and vestibular afferents.

Lewy body-like hyaline inclusions in the soma and swollen, cord-like cell processes are characteristic alterations of the anterior horn cells in familial amyotrophic lateral sclerosis (ALS) with posterior column and spinocerebellar tract involvement. A fine structural analysis of these two structures has been performed in two brothers from a family ("C" family) previously described by Kurland and Mulder in 1955. The perikaryal hyaline inclusions consisted of accumulations of randomly oriented neurofilaments interspersed with thick linear densities associated with granular material. Some of the accumulations showed a central condensation. Cord-like, swollen neuronal processes were composed, for the most part, of numerous neurofilaments arranged parallel to the long axes. Dense structures were sometimes observed within the large bundles of filaments. They were composed of ill-defined dense, granular and fibrillar material associated with scattered vesicles and mitochondria. These dense areas were sometimes surrounded by various amounts of fine filaments, approximately 5 nm in diameter.

Utilizing cyto-, myelo-, and chemoarchitecture as well as connectional criteria, the present study reveals the interstitial system of the spinal trigeminal tract (InSy-SVT) in the rat to be composed of five morphologically and functionally distinct components that are distributed within spatially restricted regions of the lateral medulla. The first component is represented by scattered interstitial cells and neuropil, which extend laterally into SVT from the superficial laminae of the medullary dorsal horn (MDH). The second component, the dorsal paramarginal nucleus (PaMd), consists of a small group of marginal (lamina I)-like neurons and neuropil situated within the dorsolateral part of SVT at the rostral pole of MDH. The third component represents a trigeminal extension of the parvocellular reticular formation (V-Rpc) into the ventromedial aspect of SVT at levels extending from rostral MDH to the caudal part of trigeminal nucleus interpolaris (Vi). The fourth component, the paratrigeminal nucleus (PaV), consists of a large accumulation of neurons and neuropil situated within the dorsal part of SVT throughout the caudal half of Vi. The fifth component is the insular trigeminal-cuneatus lateralis nucleus (iV-Cul), which is a discontinuous collection of neurons and neuropil interspersed among fibers of SVT as well as wedged between it and the spinocerebellar tract. Thalamic projection neurons are located in PaMd and V-Rpc, whereas cerebellar projecting neurons are confined to iV-Cul.

The origin of cerebellar afferents was studied in various types of reptiles, viz., the turtles Pseudemys scripta elegans and Testudo hermanni, the lizard Varanus exanthematicus, and the snake Python regius, with retrograde tracers (the enzyme horseradish peroxidase and the fluorescent tracer “Fast Blue”). Projections to the cerebellum were demonstrated from the nucleus of the basal optic root, the interstitial nucleus of the fasciculus longitudinalis medialis, the vestibular ganglion, and the vestibular nuclear complex, two somatosensory nuclei, viz., the descending nucleus of the trigeminal nerve and the nucleus of the dorsal funiculus, the nucleus of the solitary tract, the reticular formation, and throughout the spinal cord. A distinct bilateral projection to the cerebellum was found to arise in a nucleus previously called nucleus parvocellularis medialis (Ebbesson, ′67). In the present study this cell mass is termed the perihypoglossal nuclear complex, considering its comparable position and fiber connections to the perihypoglossal nuclei in mammals. In all reptilian species studied a contralateral cerebellar projection of a cell mass located in the caudal brainstem adjacent to the nucleus raphes inferior was observed. It seems likely that this cell mass represents the reptilian homologue of the mammalian inferior olive. Most of the spinocerebellar fibers appeared to arise in neurons located in area VII-VIII of the gray matter. In this respect the origin of the spinocerebellar projection in reptiles resembles the origin of the rostral and ventral spinocerebellar tracts in mammals. No indications for the existence of a column of Clarke or a central cervical nucleus in the reptilian spinal cord were obtained. On comparison of the cerebellar afferents in reptiles with the known connections of the cerebellum in amphibians, birds, and mammals, a basic pattern of cerebellar afferent projections appears to exist in these vertebrateclasses, including retinal, vestibular, precerebellar, somatosensory, and spinal afferents.

Short-latency somatosensory evoked potentials were recorded from 23 cats with the frontal-neck, scalp-ear and scalp-noncephalic reference montages. In the frontal-neck recordings, four or five components (n9, n11, n13a, n13b and n14) were identified, whereas three components (p15, p18 and p20) were recorded in the scalp-ear leads. The noncephalic reference recordings had four to six components (p9, p10, p11, p13a, p13b and p14). The origin of these components was investigated by recording direct from the attributed generators and examining the effects of lesions. The suggested generators are as follows: n9, p9 and p10-peripheral nerve; n11, p11-dorsal column; n13a-segmental dorsal horn; p13a-spinocerebellar tract; n13b and p13b-cuneate nucleus and caudal part of the medial lemniscus; n14, p14 and p15-rostral part of the medial lemniscus; p18-thalamocortical radiation; p20-primary somatosensory cortex. Components with similar latencies such as n13a and p13a in the frontal-neck and noncephalic reference recordings had different generators. In the noncephalic reference recordings, the axially orientated dipoles, including the potential produced by the spinocerebellar tract (p13a) were clearly detectable, but the transversely orientated dipole of the segmental dorsal horn (n13a) was indistinct. The frontal-neck montage was distorted by the frontal 'reference' electrode active for part of the axially ascending volleys (p13a in some cats and p14), but could pick up the near-field potentials in the segmental dorsal horn (n13a). Desynchronized volleys in fibre tracts such as the spinothalamic tract did not contribute significantly to the potentials recorded from the skin, whereas the synaptic potential in the cuneate nucleus was shown to have a steep onset and open-field distribution with its dipole orientated in part axially, and was recorded in the noncephalic reference montage. The p9 and p11 positivities fused after laminectomy, suggesting that conductance change at the root entry to the bony spinal canal separates these components in the noncephalic reference recording.

Steady state visual evoked responses were studied in a patient with the clinical diagnosis of Friedreich’s ataxia. Ophthalmologic examination revealed no anomalies including visual acuity of 6/6 in both eyes, full visual field in both eyes, normal screening color vision, absence of optic atrophy and absence of nystagmus. Steady state VER revealed a monocular moderately attenuated signal in the left eye at 12 and 16 Hz and a markedly attenuated signal at 20 and 25 Hz. This contrasted with a normal VER in the right eye. The patient died of cardiac failure secondary to cardiomyopathy associated with Friedreich’s ataxia. Autopsy examination of the brain revealed a number of structural changes. The spinal cord had the usual severe demyelination and axonal changes associated with Friedreich’s ataxia. Histologic examination of the optic nerves showed no abnormality in the right nerve but focal axonal swelling, and some evidence of demyelination in the left optic nerve.

Summary The latency from the stimulus (S) to the IS and SD components of the antidrmic spike was measured in motoneurones and spinocerebellar tract cells following displacement of the membrane potential either by current pulses or by synaptic potentials. Changes in the latency to the SD spike (S-SD delay) were mainly caused by changes in the IS-SD delay and varied from 10 to 100 μsec per mV change in membrane potential, depending on the initial value of the IS-SD delay. Changes in the S-IS delay were also observed and these changes could, especially in spinocerebellar cells, give a significant contribution to the change in the total delay. EPSPs shortened the S-SD delay as efficiently as current-evoked depolarizations of similar magnitude while IPSPs were often more effective in prolonging the delay than current-evoked hyperpolarizations. This difference was related to the larger conductance increase during IPSPs than during EPSPs and to the longer IS-SD delays at hyperpolarized potentials. The presented data contribute to the understanding of the method which uses extracellular recording of antidromic latency changes as an indirect measure of intracellular membrane potential changes. Our results show that the recording of antidromic latency changes is a particularly sensitive method for detecting inhibition of neurones.

The pathology of the central nervous system (CNS) in a dog with giant axonal neuropathy (GAN) is presented. Swollen axons containing excessive and disorganised neurofilaments were present in the spinal cord, mainly at the distal portions of long tracts. The fasciculus gracilis and dorsal spinocerebellar tracts were affected only in the rostral cervical cord while the lateral cortico spinal tract was principally involved in the lower thoracic and lumbar cord. Occasional swellings were also found in the central dorsal columns of the rostral lumbar segments and in the dorsal and intermediate grey matter. The nuclei gracilis and cuneatus, restiform body and ventral spinocerebellar tracts were all involved in the brain stem. Spheroids were seen in the white matter of the rostral cerebellar vermis and in the granule cell layer. The brachium of the superior colliculus contained swollen axons and the cortex was diffusely involved with spheroids. The distribution was of a distal axonopathy and the cortical changes provided an explanation for the abnormal EEG and mental retardation found in some human patients.

An anatomical technique based on the retrograde transport of horseradish peroxidase (HRP) was used to investigate the projections of spinal cord neurons to the reticular formations in the rat. Both large and restricted injections were staggered all along the bulbar and pontine levels, involving the nucleus gigantocellularis, the nuclei reticularis pontis, pars oralis and caudalis and in some cases the nucleus raphe magnus. Labeled cells were constantly encountered in the reticular part of the neck of the dorsal horn throughout the whole length of the cord, mainly contralateral to the central core of the injection site. This area was taken as the equivalent of lamina V in the cat. Other labeled cells were observed in the medial parts of the intermediate and ventral horns, in areas considered similar to laminae VII and VIII in the cat. The two most rostral cervical segments were characterized by an additional bilateral projection originating from the dorsolateral part of ventral horns. Thus, this study is a clear confirmation that the bulbopontine reticular formations constitute a target for various somatosensory inputs originating in spinal cord. It demonstrates that the medial spinoreticular tract (mSRT) differs from the other main ascending tracts by the absence of projections from (1) superficial layers and nucleus of the dorsolateral funiculus contrary to the spinomesencephalic tract; (2) ventromedial zone of the lumbar dorsal horn unlike the spinothalamic tract; (3) the neck of the dorsal horn in its medial portion contrary to the spinoreticular component reaching the lateral reticular nucleus; and (4) central cervical nucleus and Clarke's columns, unlike the spinocerebellar tracts. The difficulty in demonstrating retrograde labeling from discrete injections could result from the fact that mSRT neurons have sparsely ramified collaterals on their terminal zones.

Spinocerebellar tract (SCT) neurones in and around the central cervical nucleus (CCN) were physiologically identified by antidromic activation of these cells on stimulation of the cerebellum. Among the spinocerebellar tract cells thus identified, those ascending the contralateral spinal funiculi were found in the CCN and ventralwards, whereas those ascending the ipsilateral funiculi existed mostly dorsal to the CCN partly overlapping with crossed cells in the nucleus. Mapping sites from which CCN cells were antidromically activated showed that axons of the CCN-SCT cross at the same segment, ascend the ventral funiculus initially, the lateral funiculus at rostral C1 and the lateral border of the medulla to reach the cerebellar peduncle, enter the cerebellum mainly via the restiform body but possibly also via the superior peduncle. Systematic mapping of stimulation within the cerebellum indicated that the CCN-SCT projects to the medial part of the anterior lobe and the posterior lobe bilaterally. Projection to lobules I-II was found in almost all CCN-SCT cells examined. Three fourths of CCN-SCT cells projected to the posterior lobe, as revealed by less extensive mapping. Mapping of axonal regions of the same single CCN-SCT cells showed that they project multifocally in the cerebellum, where projection to lobules I-II was common and that to other areas varied with individual cells. Conduction velocities decreased within the cerebellum probably as the result of repeated branching. Mossy fibre responses evoked on stimulation of the C2 dorsal root in cats with the transected dorsal funiculi were shown to be mediated mostly via the CCN-SCT. Mapping the field potential showed that the response was by far the largest in lobules I-II. This suggested that the terminals provided by the CCN-SCT are the densest in these lobules.

Morphological and morphometric studies were performed on the spinal cords and roots in 6 typical cases of Werdnig-Hoffmann disease (WHD) and 3 age-matched controls to gain further insight into the pathogenesis of this disease. (1) We observed islands of glial bundles in the anterior spinal roots in all cases and in the posterior roots in one case. (2) Loss of myelin was seen in the posterior columns and spinocerebellar tracts at the thoracic and lumbar segments in two cases, and in the anterior and lateral corticospinal tracts at the thoracic and lumbar segments in one case. (3) A few figures of neuronophagia were observed in the Onufrowicz nuclei in two cases, whereas the figures were hardly seen in other nuclei. (4) a) In the lateral nuclei of C5, L3 and S2 segments of the spinal cords in WHD, the reduction in the number of motor cells was almost symmetrical and diffuse throughout the spinal cord, and it varied from one-eleventh to one-third of controls. b) In the anteromedial nuclei of C5 and L3 segments, there was mild to moderate reduction in the number of motor cells (50–75% and 36–72% of controls, respectively). c) There was no distinct difference in the number and the mean diameter of the cells in the Onufrowicz nucleus between WHD and controls, but some of the cells of the nucleus in WHD showed central chromatolysis (3.1–4.9%) to the same extent as those of other nuclei. d) In controls, the mean minimum diameter of the cells of the lateral, anteromedial and Onufrowicz nuclei was comparatively large, medium and small, respectively. These results suggested a tendency to initial degeneration of the clusters of the large motor cells and later degeneration in those of the small or medium cells in WHD. However, the cause remains unknown.

The projection fields of spinal border cells (SBCs) in the cerebellar anterior lobe were studied using the anterograde transport of wheat germ agglutinin bound to horseradish peroxidase in the cat. Many anterogradely labeled terminals of the SBCs were seen in the apical to middle parts of sublobules IIb-Va on the side ipsilateral to the injection. In the mediolateral extent they were distributed densely in areas in the lateral part of the vermis (zone B) to the intermediate-lateral part of the lobules (zones C1-D). The present study suggests that the SBCs project, predominantly ipsilaterally, to specific parts of sublobules IIb-Va.

Extracellular and intracellular recordings were made from spinocerebellar tract neurones of the central cervical nucleus (CCN) in C1-C3 segments of the anaesthetized cat. These neurones were identified by antidromic activation from the cerebellar peduncle. Stimulation of the ipsilateral dorsal root elicited extracellular spikes or EPSPs with a monosynaptic latency in almost all CCN neurones in the same segment (segmental input). Late excitatory effects were also observed in about one third of CCN neurones. The monosynaptic EPSP was occasionally followed by an IPSP. The excitatory input from the dorsal root to CCN neurones was extended over several segments for some CCN neurons (extrasegmental input). Monosynaptic excitation was evoked in CCN neurones after stimulation of dorsal neck muscle nerves as well; i.e. splenius (SPL), biventer cervicis and complexus (BCC), rectus capitus dorsalis, and obliquus capitus caudalis. Thresholds for this excitation were near the threshold of the nerve, suggesting that it originated from group I fibres. The component of excitation added after strong stimulation of neck muscle nerves would be attributed to group II fibres. When a CCN neurone received excitatory input from the nerve of one muscle, it was generally not affected by stimulation of other nerves in the same segment. Such muscle specificity of segmental input was the principal pattern of connexion of neck muscle afferents with CCN neurones. In some cases, however, excitatory convergence from SPL and BCC nerves onto single CCN neurones or excitation from the SPL nerve and inhibition from the BCC nerve were also observed. Nearly half of the CCN neurones received input from one muscle nerve of the same segment and not from the afferent of the same muscle of different segments, indicating a segment specificity of input. In the remaining CCN neurones, weaker excitatory effects were induced from afferents of different segments as well. In such extrasegmental effects, inputs to CCN neurones from caudal segments predominated in frequency over those from rostral segments. The origin of extrasegmental input was generally confined to the same muscle. Low threshold muscle afferents from the SPL and BCC were intraaxonally stained with HRP. The collaterals of the stained fibre distributed branchlets and terminals to the CCN, laminae VII, VIII, and motor nuclei. Two fibres responding to local muscle prodding or stretch showed a similar morphology. The findings indicated that muscle spindle afferents from primary endings projected to the CCN.

The ascending spinal systems in the nurse shark were studied after spinal hemisections by use of the Nauta and Fink-Heimer techniques. The dorsal funicular fibers form a single bundle issuing fibers to the gray substance of the spinal cord, the dorsal funicular nucleus, and the vestibular complex. Some dorsal funicular fibers also appear to contribute to the spinocerebellar tract. The degenerated lateral funicular fibers are segregated into three fasciculi issuing fibers medially as they ascend through the brainstem. The largest target of these fibers is the reticular formation, but diffusely organized axons also reach 1) the gray matter of the spinal cord, 2) the dorsal motor nucleus of the vagus, 3) the nucleus "A" of the medulla oblongata, 4) the central gray substance of the brainstem, 5) the cerebellar cortex, 6) the cerebellar nucleus, 7) the nucleus intercollicularis, 8) the mesencephalic tectum, and 9) the dorsal thalamus. At the latter site the spinal input appears to partly overlap with the visual input. The results, compared with the strikingly similar findings in other classes of vertebrates, indicate that all vertebrate groups apparently have the same basic components of ascending spinal projections.

Spinocerebellar projections were studied in the turtle, Pseudemys scripta elegans, by both anterograde (injections of 35S-methionine into various spinal segments) and retrograde (injections of horseradish peroxidase into the cerebellar cortex) tracing techniques. After unilateral HRP injections, labeled neurons were found on both sides of the spinal cord. The total number of retrogradely labeled spinocerebellar tract neurons was relatively small and neuronal aggregations were not observed. Most spinocerebellar tract neurons were found in the ventral horn, dorsal to the motoneuronal cell group. Some cells lay in the spinal intermediate zone and in the dorsal horn. The fibers mainly ascended in the lateral funiculus, some in the ventral and possibly some in the dorsal funiculi. Spinal projections terminated within the cerebellar granular layer. The spinocerebellar target area extended along the whole medio-lateral extent and covered about the rostral four fifths of the cerebellar plate. Individual target areas, separated from each other, as are the anterior and posterior spinocerebellar target areas of higher vertebrates, could not be identified. Similar to mammals, however, the terminal field in the turtle was not a homogenous one but consisted of zones of mossy fiber terminations of varying sizes and intensities.

Cell populations of the lumbar ventral horn, the gracile and cuneate nuclei and also the cells of origin of the spinocerebellar tract have been studied in the adult mutant ‘mutilated foot’ ( mf ) rat. This mutant is affected by a severe congenital reduction in numbers of dorsal root ganglion cells. The present study has shown that the secondary neurons in the dorsal column nuclei are also reduced in number. Lumbar motor neurons of the mf rat were counted and measured after labelling by retrograde transport of horseradish peroxidase from the sciatic nerve and from injection into leg muscles. Fewer motor neurons of small size were present in the mf , in agreement with the previous finding of a reduced population of small myelinated (presumably gamma efferent) fibres, which is consistent with the lack of muscle spindles. Reconstructions of lumbar motor neurons showed a population of cells which were larger than normal. The size, localization and density of cells of origin of the spinocerebellar pathway were studied by retrograde labelling of these cells by intra-cerebellar injection of horseradish peroxidase. No differences seem to be present between mf and control rats despite the fact that in the mutant there is a progressive degeneration of spinocerebellar tracts. The absence of small motor neurons and the increase in volume of the large motor neurons is consistent with earlier observations in the ventral root of the mf rat of a decreased number of small axons and the presence of abnormally large axons. It is suggested that the reduction in dorsal column cells is a consequence of the reduced input from the primary sensory neurons. Likewise, the dorsal and ventral spinocerebellar tract degeneration may possibly be a consequence of the lack of sensory input to the cells of origin of this tract.

Following injections of horseradish peroxidase into the cerebellum, the distribution of labeled neurons was studied in the whole length of the spinal cord of the rat. To find the ascending side of the axons, injections were made following hemisections at C1 or between C1 and C2. Labeled spinocerebellar tract neurons were classified into two groups according to the axonal course in the spinal cord; one is composed of neurons with uncrossed ascending axons and the other, neurons with crossed ascending axons. Neurons of origin of the uncrossed tracts were located in the medial part of lamina VI of C2 to C8, the central part of lamina VII of C4 to C8, lamina V of C7 to L3 and Clarke's column. Neurons of origin of the crossed tracts were found in the central cervical nucleus of C1 to C3, the intermediate zone and the ventral horn of the lower thoracic and the lumbar segments (T11 to L3), and in the dorsal horn, the medial part of lamina VII and the ventrolateral part of the ventral horn of the sacral and caudal spinal cord. In comparison with our previous results in the cat, it was suggested that the spinocerebellar system in the rat is organized in the same fashion as in the cat, in terms of the location and the intraspinal axonal course of the cells of origin.

The transport of HRP into the spinal cord and medulla in the cat has been examined from a forelimb cutaneous nerve, the lateral superficial radial nerve (LSR), and from the muscle nerves supplying both heads of the forelimb muscle, extensor carpi radialis (ECR). HRP transported by the LSR was widely distributed in the spinal cord throughout laminae I-IV in the vicinity of the root entry zone and from spinal segments T1 to C5. HRP was also transported from the LSR to the medulla where there was intense patchy, discontinuous labelling in the main cuneate nucleus. The pattern of labelling in the cuneate nucleus did not follow any simple somatotopic plan. Exposure of the muscle nerve to HRP led to labelling in the spinal dorsal horn in lamina I, in the deep dorsal horn on the lamina V/VI border, and in lateral and medial lamina VI at sites that contain cells of origin of spinocerebellar tracts. The medial lamina VI label was contiguous with a deposit that extended medially to the central canal. The label in lateral lamina VI was patchy and formed a discontinuous column from T1 to C5. HRP transported by the muscle nerve also produced label in the more ventral regions of the cuneate nucleus where it had a lacy appearance, in part due to its extensive distribution around dendrites. A relatively dense, patchy, and discontinuous deposit of reaction product was also present in the external cuneate nucleus after muscle nerve exposure. This deposit was most intense on the dorsomedial surface of this nucleus, but another, less intense, deposit was also present ventrally.

The responses of spinocerebellar tract neurons in the CCN to natural stimulation of vestibular and neck muscle receptors were investigated in decerebrate cats. The spike activity of single CCN neurons was recorded extracellularly with a floating microelectro-de in the C2 segment of the spinal cord. CCN neurons exhibited clear modulation of firing activity in response to sinusoidal rotation of the head in the vertical planes but not to rotation in the horizontal semicircular canal plane. The response to vertical rotation was attributed to stimulation of the vertical semicircular canals, since selective stimulation of otolith organs by static tilt of the head in the same plane had no effect. The response was approximately in phase with the head angular velocity at 0.05–2.0 Hz. Vector analysis suggested that the optimal orientation of vertical rotation varied considerably among neurons. The CCN neurons increased or decreased their firing rate in response to stretch of dorsal neck muscles. The time course of the responses suggested that muscle spindle primaries were most likely to be the receptors responsible for both excitatory and inhibitory responses. The input was highly muscle specific in that most CCN neurons received excitation from one muscle or two synergists, and that a group of neurons was specifically inhibited from biventer cervicis and complexus. The vestibular and neck muscle afferent signals converged with specific patterns of combination on individual CCN neurons. It is suggested that each CCN neuron integrates signals from the labyrinth and the neck and provides the cerebellum with information concerning the head movement in a certain vertical direction.

1. Neurones in the lateral reticular nucleus (LRN) activated by the bilateral ventral flexor reflex tract (bVFRT-LRN neurones) were identified by their responses to stimulation of fibres descending in the contralateral ventral quadrant of the spinal cord which activate the bVFRT neurones monosynaptically. 2. Eighty-eight of the 134 bVFRT-LRN neurones encountered could be antidromically activated at a low stimulus strength from small areas of the cerebellar surface assumed to represent cortical termination points. 3. The bVFRT-LRN neurones occurred throughout the parvi- and magnocellular parts of the LRN and terminated bilaterally in the anterior lobe and sparsely in the ipsilateral paramedian lobule and in the pyramis. 4. The responses evoked in the bVFRT-LRN neurones on stimulation of the contralateral ventral quadrant at C5 and L1 made it possible to estimate the approximate spinal level from which the bVFRT fibres originated. On this basis the bVFRT-LRN neurones were divided into cervical, thoracic, and lumbar groups receiving bVFRT afferents from mainly one spinal level and a convergence group receiving bVFRT afferents from several levels. 5. The different bVFRT-LRN groups received excitation from different combinations of nerves in the four limbs. 6. The cervical, thoracic and lumbar groups of the bVFRT-LRN neurones occurred in successively more ventrolateral portions of the LRN. 7. The cervical, thoracic and lumbar groups of the bVFRT-LRN neurones terminated in successively more rostral areas of the anterior lobe. 8. The organization of the bVFRT-LRN path is compared with that of the ventral and rostral spinocerebellar tracts. The possible function of the bVFRT-LRN path is discussed.

Classical beliefs about the functions of the dorsal columns of the spinal cord have been attacked following recent evidence that position and vibration sensations may be carried in the dorsal spinocerebellar tracts. There is evidence that the one specific function of the dorsal columns is for the transmission of information concerning the direction of tactile cutaneous movement. Thirty normal controls, 43 patients with spinal cord disorders and 10 patients with functional disorders were examined prospectively using an easily administered "direction of scratch" protocol. Interpretation of the direction of a 2 cm vertical tactile cutaneous movement over the lower limbs was found to be accurate in normal controls and grossly inaccurate in patients with functional disorders, exceeding the error rate of guessing. Detection of direction of 2 cm scratch was moderately impaired in 11 of 13 patients with spastic paraparesis and preserved sensation to all other modalities and 23 of 24 patients with spastic paraparesis and impaired proprioception and/or vibration sensations. Direction of 2 cm scratch, proprioception and vibration sensations were preserved in the three cases with anterior spinal cord syndromes. It is proposed that tactile perception of direction of 2 cm scratch over the lower limbs is a sensitive sign of posterior column function which can be usefully incorporated into the clinical sensory examination in the evaluation of spinal cord disorders.

Holmqvist, B. and O. Oscarsson. Location, course, and characteristics of uncrossed and crossed ascending spinal tracts in the cat. Acta physiol. stand. 1963. 58. 57—67. — Discharges evoked in coarsefibred ascending spinal tracts on stimulation of muscle and skin nerves in the hindlimbs and on stimulation of lumbar, sacral, and caudal dorsal roots, were recorded from dissected fascicles of the cord at L1 and C3. Tracts in the dorsal part of the lateral funiculus are monosynaptically activated only from ipsilateral afferents and tracts located ventrally thereof only from contralateral afferents (exceptional findings on stimulation of the most caudal roots are related to the crossing of primary afferents in these caudal segments). It is concluded that the former tracts are uncrossed and the latter crossed at the spinal level. — There is no obvious segmental lamination of fibres within the areas of uncrossed and crossed tracts. Individual tracts occupy relatively fixed and well defined areas independent of their level of origin. There is a marked dorsal shift of the dorsal and ventral spinocerebellar tracts during their ascent in the cord.

IN THE ADULT, motor neuron disease or amyotrophic lateral sclerosis can be subdivided into several groups on the basis of clinical, pathologic, and epidemiologic features. 1 The histologic changes observed in the classic sporadic cases include nonspecific degeneration and loss of motor neurons in the spinal cord, brain stem, and cerebral cortex. Demyelination of the pyramidal tracts often accompanies the neuronal losses. 2 A familial variant further characterized by demyelination of the posterior columns and spinocerebellar tracts has been reported. 3 In a few residual motor neurons from these cases, Hirano et al 4 described accumulations of hyalinized material, occasionally with acidophilic cores that resemble Lewy bodies. In still another variant, the amyotrophic lateral sclerosis and Parkinsonism-dementia complex on Guam, neurofibrillary tangles have been observed in the anterior horn cells. 5 This report presents light and electron microscopic observations from an unusual sporadic case of motor neuron disease characterized by

Recent anatomical and physiological investigations have supplied a basic knowledge of the organization of the cerebellar cortex and its efferent paths (Eccles, Ito and Szentagothai, 1967). Understanding of cerebellar function requires also knowledge of the afferent paths and the information carried by them. This chapter surveys the present knowledge about the spinocerebellar paths activated by somatic afferents. These paths are better known than those activated by visceral afferents (Dow and Moruzzi, 1958; Newman and Paul, 1969) and the afferent paths from higher brain centres (Jansen and Brodal, 1958; Evarts and Thach, 1969).

The cells of origin of the ventral spinocerebellar tract have never been determined conclusively. We attempted to determine the cell origin of this tract by applying anatomical methods. Retrograde changes were observed in the lumbosacral segments following hemicerebellectomy, severance of cerebellar peduncle or hemisection of spinal cord at various levels. The chromatolytic motor-type neurons were plotted, most occupying the dorso-lateral portion of the ventral gray, with fewer cells in the medial, lateral and central part of ventral horn. Ablation of these neurons in different animals resulted in axonal degeneration which could be traced to the cerebellum via chiefly contralateral lateral funiculus and from the ventral spinocerebellar tract. The morphology of the ventral spinocerebellar tract neurons was studied by the Golgi method. Incidental findings of axonal degeneration bilaterally in the dorsal spinocerebellar tracts, with ipsilateral domination, following ablation of the ventral spinocerebellar tract neurons were discussed.

Rhizotomy of the dorsal roots of the upper limb in lesioned monkeys with lesioned-induced and harmaline-induced tremor caused complete anaesthesia and akinesia of the corresponding limb, which only showed purposeless movements. The rate and rhythm of postural tremor and the reciprocality of the bursts in opposite muscles were not affected by the rhizotomy; the incidence of tremor episodes was greater in some animals. Rhizotomy apparently interfered with the amplitude of the bursts which, at times, was less regular in the deafferented limb. In four out of six animals the rhizotomy involved the blood supply of the dorsal part of the lateral column. This caused a degeneration of the corresponding lateral corticospinal and dorsal spinocerebellar tracts, producing a weakness of the ipsilateral lower limb which gradually improved. Faster bursts (12–13/sec) were also noted on the EMG in response to harmaline in monkeys with cerebellar lesions. These findings suggest that the influence transmitted through the spinal dorsal roots does not play an important role in initiating postural tremor. The rate and rhythm of tremor episodes are uninfluenced by impulses transmitted through the dorsal roots which, however, apparently exert a stabilizing effect on the amplitude of the bursts.

1.) Enzootic ataxia or swayback has been related to Schildcr's disease -- which is of course closely related to disseminated sclerosis -- because of the fact that one sometimes sees in the ataxia of lambs a gelatinous appearance of the white matter (INNES 1939). To be more precise it is the infantile form of Schildcr's disease that has been most frequently cited in this regard (MAc]~A~ i940; WIN]~ELmAN and MooRE 1942; INNES 1943) but INNES and SAUN])EI~S have more recently (1957) stated that "this does not however imply any causal relationship". 2.) Swayback would appear to be a demyelinating disease forming from the pathogenctic point of view part of a generalized disorder -- which may possibly also be local -- involving a disorder of copper metabolism (BE~ETS 1937). It is an attempt to co-ordinate these morphological analogies and the disorders o/ metabolism involved which forms the starting point of the histopathological and biochemical research that we have undertaken as a team in the last five years. In this work we shall only discuss the histopathological findings. Our observations concerning the animals originate in regions as different as those of Thessalonica (Greece) and Reykjavik (Iceland). This is not without interest nor is it unintentional. One must ask oneself wheter there are not differences between the ataxia of lambs observed in England and in Greece and those described in South Africa, in New Zealand andin Australia. Geographical variations can perhaps explain why different observers have published series in which the frequencies and the qualities of the lesions have been very variable. These variations are of such a degree that one sometimes asks oneself whether ~he descriptions do really correspond to identical morbid entities. The first lesions seen by BENN~T (1932) were described as degenerations of fibres in the thoraeo-iumbar spinal cord and in the sciatic and femoral nerves. Some cases with more protracted evolution showed a sclerosis of the spinal cord. These spinal cord lesions were localised, according to STEWART (1932), in the spinocerebellar tracts and in the column of GoU and were accompanied by anomalies of the cells of the column of Clarke in the thoracic cord.

Twenty-one members of a family through four generations have experienced a syndrome similar to amyotrophic lateral sclerosis, with additional features of sensory loss and prolonged course. Five patients were examined, two of whom had glove and stocking distribution of sensory impairment. Autopsy on one showed demyelination and gliosis in the spinocerebellar tracts and in Goll's tracts of the posterior columns in addition to similar changes and loss of cells in the anterior horns. The average course lasted more than 11 years. Two other cases presented as progressive muscular atrophy without signs of spasticity. All other cases consistently began with leg weakness, followed by arm and bulbar weakness, with signs of both upper and motor neuron degeneration. The mode of transmission was autosomal dominant with complete penetrance.

A total of 21 domestic pigs were used in a study of spinal cord fiber systems which subserve a pain response in the pig. Distribution of fiber systems were determined by the placement of various lesions into the spinal cord and examining the animal for its ability to give a complete pain response. The Swank-Davenport modification of the Marchi technique for staining degenerating myelnated fibers was used to determine the pattern of trajectory of myelinated fibers along the spinal cord. Lesions were made at the cervical level in three animals and resulting pattern of degenerating fibers was compared with those of the other animals in which the lesions had been placed at lower thoracic levels. In most animals the lesions were limited to a single site on the spinal cord, but in six animals staggered, bilateral hemisections were made to determine whether or not these fiber systems are as diffuse in the pig as has been reported for the cat. The spinal cord fiber systems which subserve a pain response in the pig are located generally within the ventrolateral quadrant of the spinal cord. It was found that only a small portion of one lateral funiculus just ventral to the dorsal and ventral spinocerebellar tracts, if left intact, was sufficient for the elicitation of a pain response from either rear limb. The results presented here indicate that the fiber systems in the spinal cord of the pig which subserve pain responses are more diffuse than in carnivora or in primates.

The morphology and temporal course of degeneration of the mossy fibers in the cerebellum of the cat have been studied following transection of the dorsal and ventral spinocerebellar tracts or both, at various levels of the spinal cord. The silver-impregnation methods of Nauta and Gygax, of Nauta (using the Laidlaw solution), of Glees and of Reumont-Lhermitte have been used on 20-μ sagittal sections through the cerebellar vermis. The four methods give concordant results, although the pictures obtained are not entirely identical with all of them. As early as 50 hours after the lesion, degeneration is in progress in the parent fibers in the white matter as well as in the mossy fiber terminals in the granular layer. While the latter have largely disappeared 63 days after the lesion, degenerating fibers in the white matter are still present after 122 days. The degeneration of the terminal formations begins with an increased argyrophilia and some swelling of the terminal boutons, which appear as solid globules. The fine fibers leading up to them disintegrate and soon disappear. The argyrophilic globules appear finally to fall apart into minute fragments. Attention is drawn to the occasional occurrence in normal as well as experimental animals of groups of argyrophilic globules in the granular layer, resembling degenerating mossy fiber terminals. The reason for the appearance of this “spontaneous” degeneration is obscure. It is suggested that it may be due to some process, affecting primarily the terminal formations of the mossy fibers.

A spinocerebellar tract activated from ipsilateral forelimb nerves has been identified by antidromic activation from the cerebellar cortex. This tract has been denoted the rostral spinocerebellar tract (RSCT). It originates from cell bodies at, or slightly above, the level of the dorsal roots supplying excitation. The RSCT ascends in the middle third of the lateral funiculus where it has a more ventral position than the ventral spinocerebellar tract (VSCT) which it partly overlaps. About two thirds of the RSCT enter cerebellum together with the VSCT through the brachium conjunctivum. About one third of the RSCT shifts dorsally, becomes contiguous to the dorsal spinocerebellar tract (DSCT), and enters cerebellum through the restiform body. The RSCT terminates mainly in the anterior lobe but some fibres send branches also to the pyramis and the ipsilateral paramedian lobule. In the anterior lobe the RSCT terminates in bilateral zones consisting of a medial strip of the intermediate cortex and a lateral strip of the vermal cortex. The termination is more intense ipsilaterally and the fibres reach equally often the “hindlimb” as the “forelimb area”. — The RSCT receives monosynaptic excitation from high threshold group I muscle afferents and polysynaptic excitation from the flexor reflex afferents. The functional organization and the characteristic cerebellar termination suggest that the RSCT is a forelimb equivalent of the VSCT.

A case is reported which combines the changes of motor neurone disease with posterior column degeneration and spinocerebellar tract degeneration. The surviving perikarya of the anterior horn neurones showed intracytoplasmic hyaline material which was feebly argyrophilic. Electron microscopy of this abnormal material showed it to consist of bundles of neurofilaments approximately 10 nm in diameter and morphologically similar to normal neurofilaments. The literature of the ultrastructure changes in various neurological system degenerations and in experimentally-induced neurofibrillary degenerations is reviewed.

1. Extra- and intracellular recording has been made in cats from the spinal border cells (SBCs) of Cooper and Sherrington (1940). The SBCs were identified by their location in the lateral part of the ventral horn in the lumbar segments 3–6 and by their antidromic invasion from the contralateral thoracic spinal cord. 2. The conduction velocity of SBC axons ranged from 40–140 m/sec with a mean of 85 m/sec. 3. Lesion experiments showed that the SBC axons ascend in the ventrolateral region of the spinal cord. 4. Of 90 SBCs tested, 85 were invaded antidromically by stimulation of the cerebellar cortex. 5. It is concluded that SBCs give rise to ventral spinocerebellar axons and suggested that they are the major source of this tract.

The site of lesions in Miller Fisher syndrome, especially those causing ataxia, has been controversial. A 50 year old man with features of Miller Fisher syndrome in whom MRI showed enhancing lesions in the spinocerebellar tracts at the level of the lower medulla is reported. Peripheral involvement of cranial nerves was also indicated by an abnormal blink reflex and by clinical manifestations: complete external ophthalmoplegia, bilateral peripheral facial weakness, convergence disturbance, absence of Bell's phenomenon, oculocephalic, and oculovestibular reflex. Abnormal lesions on MRI disappeared and the blink reflex became normal with clinical improvement. The case is regarded as Miller Fisher-Guillain-Barré overlap syndrome, a postinfectious allergic reaction involving both peripheral nerves in the cranium and neuraxis in the spinocerebellar tract. The lesions in the spinocerebellar tracts are responsible for cerebellar ataxia in this syndrome.

The present study aimed to assess spinal tract formation in neurons originating from cervical (C7), brachial (C14), and thoracic (T4) regions, with the lumbar (LS2) region as a reference, in a chick embryo. For the assessment of the spinal tracts, we introduced a vector expressing human placental alkaline phosphatase into progenitor cells generated after neural tube closure and belonging to the above segments, using in ovo electroporation. The ascending axons took primarily similar paths: dorsal commissural, ventral commissural, and dorsal non-commissural paths, with some variance depending on their originating segments. Some populations of non-commissural neurons later extended their axons following a ventral path. The elongation rates of these axons are primarily constant and tended to increase over time; however, some variations depending on the originating segments were also observed. Some of the dorsally ascending axons entered into the developing cerebellum, and spinocerebellar neurons originating from T4 projected their axons into the cortex of the cerebellum differently from those from LS2. These results unveil an overall picture of early ascending spinal tract formation.

An analysis of genetic fitness was performed in Huntington's Disease (HD) and Spinocerebellar Ataxia 1 (SCA1) families. Two partially overlapping samples were used: clinically defined HD and SCA1 patients from families ascertained in definite geographical areas, and molecularly typed carriers of HD and SCA1 mutations (CAG trinucleotide expansions). In both cases, a control group of normal relatives was used. HD and SCA1 patients born before 1915-20 had more children than normal controls. Carriers of HD and SCA1 mutations, all in the low/medium expansion range (37-49 and 47-54 CAG repeats respectively), had a higher number of children than controls up to more recent times (1935-1950). The reproduction of heterozygotes for large expansions could be analysed only in subjects born after 1950 and provided indirect evidence of a lower than normal number of children. The above results fit a model based on a differential fitness according to the degree of expansion. Such a model predicts that 1) up to relatively recently the frequency of alleles in the low/medium range has been maintained or even increased by the increased fitness of their carriers, as well as by new mutations, and 2) the frequency of large expansions, part of which are lost at each generation, is maintained through further expansions of alleles in the low/medium expansion range. The implications of such a model on linkage disequilibrium and the possible spread of these diseases in future generations are discussed.

INVESTIGATIONS of the fine structure of synaptic junctions have revealed a morphological differentiation of apposed synaptic membranes and associated presynaptic and postsynaptic elements1–4. Presynaptic terminals have been shown to contain agranular synaptic vesicles, although larger granular vesicles have also been reported5,6. Two kinds of axonal terminals were recently identified, one of which contains spherical, and the other flattened, agranular vesicles. The observation was made in boutons synapsing with dendrites in the molecular layer of the cerebellum7 and in boutons synapsing with anterior horn cells of the spinal cord8. This communication reports observations on two forms of synaptic vesicles which can be used to differentiate two types of boutons found within Clarke's column of the monkey (Saimiri sciureus). This nucleus of the dorsal column is found in the spinal cord at thoracic and upper lumbar levels. It receives proprioceptive impulses chiefly from neuromuscular spindles and Golgi tendon organs. These impulses are relayed to the cerebellum by spinocerebellar tracts.

Generators of median short-latency somatosensory evoked potentials were studied with three orthodiagonal pairs of bipolar electrodes. N11 was attributed to the dorsal root and dorsal column volleys. N13 had at least two subcomponents, generator dipoles of which are directed horizontally (N13a) and axially (N13b). N13a was generated in the lower cervical cord. N13b (bipolar) and P14 far-field (noncephalic reference) appeared to originate in the cuneate nucleus or spinocerebellar tracts as well as in the medial lemniscus. Bipolar recordings were useful in localizing cervical cord lesions, which was impossible in conventional monopolar recordings.

Based on a clinical, pathologic, and genetic study of 14 families, at least three types of familial motor neuron disease can be distinguished, all apparently of autosomal dominant transmission. The first is characterized by rapid, progressive loss of motor function with predominantly lower motor neuron manifestations and a course lasting less than 5 years. Pathologic changes are limited to the anterior horn cells and pyramidal tracts. The second type is clinically identical to the first, but at autopsy additional changes are found in the posterior columns, Clarke's column, and spinocerebellar tracts. The third type is characterized by a much longer survival usually beyond 10 and after more than 20 years in affected family members but is otherwise similar to the second type.