Explore the vast range of titles available.

Key Points The cerebellum is crucial for the coordination of movement. Here, we present a model of the cerebellar paravermis, a region concerned with the control of voluntary limb movements through its interconnections with the spinal cord. We particularly focus on the olivo–cerebellar climbing fibre system. Climbing fibres are proposed to convey motor error signals (signals that convey information about inappropriate movements) related to elementary limb movements that result from the contraction of single muscles. The actual encoding of motor error signals is suggested to depend on sensorimotor transformations carried out by spinal modules that mediate nociceptive withdrawal reflexes. The termination of the climbing fibre system in the cerebellar cortex subdivides the paravermis into distinct microzones. Functionally similar but spatially separate microzones converge onto a common group of cerebellar nuclear neurons. The processing units formed as a consequence are termed 'multizonal microcomplexes' (MZMCs), and are each related to a specific spinal reflex module. The distributed nature of microzones that belong to a given MZMC is proposed to enable similar climbing fibre inputs to integrate with mossy fibre inputs that arise from different sources. Anatomical results consistent with this notion have been obtained. Within an individual MZMC, the skin receptive fields of climbing fibres, mossy fibres and cerebellar cortical inhibitory interneurons appear to be similar. This indicates that the inhibitory receptive fields of Purkinje cells within a particular MZMC result from the activation of inhibitory interneurons by local granule cells. On the other hand, the parallel fibre-mediated excitatory receptive fields of the Purkinje cells in the same MZMC differ from all of the other receptive fields, but are similar to those of mossy fibres in another MZMC. This indicates that the excitatory input to Purkinje cells in a given MZMC originates in non-local granule cells and is mediated over some distance by parallel fibres. The output from individual MZMCs often involves two or three segments of the ipsilateral limb, indicative of control of multi-joint muscle synergies. The distal-most muscle in this synergy seems to have a roughly antagonistic action to the muscle associated with the climbing fibre input to the MZMC. Our model indicates that the cerebellar paravermis system could provide the control of both single- and multi-joint movements. Agonist–antagonist activity associated with single-joint movements might be controlled within a particular MZMC, whereas coordination across multiple joints might be governed by interactions between MZMCs, mediated by parallel fibres. A coordinated movement is easy to recognize, but we know little about how it is achieved. In search of the neural basis of coordination, we present a model of spinocerebellar interactions in which the structure–functional organizing principle is a division of the cerebellum into discrete microcomplexes. Each microcomplex is the recipient of a specific motor error signal — that is, a signal that conveys information about an inappropriate movement. These signals are encoded by spinal reflex circuits and conveyed to the cerebellar cortex through climbing fibre afferents. This organization reveals salient features of cerebellar information processing, but also highlights the importance of systems level analysis for a fuller understanding of the neural mechanisms that underlie behaviour.

The spinocerebellar systems are essential for the brain in the performance of coordinated movements, but our knowledge about the spinocerebellar interactions is very limited. Recently, several crucial pieces of information have been acquired for the spinal border cell (SBC) component of the ventral spinocerebellar tract (VSCT), as well as the effects of SBC mossy fiber activation in granule cells of the cerebellar cortex. SBCs receive monosynaptic input from the reticulospinal tract (RST), which is an important driving system under locomotion, and disynaptic inhibition from Ib muscle afferents. The patterns of activity of RST neurons and Ib afferents under locomotion are known. The activity of VSCT neurons under fictive locomotion, i.e. without sensory feedback, is also known, but there is little information on how these neurons behave under actual locomotion and for cerebellar granule cells receiving SBC input this is completely unknown. But the available information makes it possible to simulate the interactions between the spinal and cerebellar neuronal circuitries with a relatively large set of biological constraints. Using a model of the various neuronal elements and the network they compose, we simulated the modulation of the SBCs and their target granule cells under locomotion and hence generated testable predictions of their general pattern of modulation under this condition. This particular system offers a unique opportunity to simulate these interactions with a limited number of assumptions, which helps making the model biologically plausible. Similar principles of information processing may be expected to apply to all spinocerebellar systems.

After spinal cord injury, tissue distal to the lesion contains undamaged cells that could support or augment recovery. Targeting these cells requires a clearer understanding of their injury responses and capacity for repair. Here, we use single nucleus RNA sequencing to profile how each cell type in the lumbar spinal cord changes after a thoracic injury in mice. We present an atlas of these dynamic responses across dozens of cell types in the acute, subacute, and chronically injured spinal cord. Using this resource, we find rare spinal neurons that express a signature of regeneration in response to injury, including a major population that represent spinocerebellar projection neurons. We characterize these cells anatomically and observed axonal sparing, outgrowth, and remodeling in the spinal cord and cerebellum. Together, this work provides a key resource for studying cellular responses to injury and uncovers the spontaneous plasticity of spinocerebellar neurons, uncovering a potential candidate for targeted therapy. Matson et al. performed single nucleus sequencing of the “spared” spinal cord tissue distal to an injury in mice. They found that spinocerebellar neurons expressed a pro-regenerative gene signature and showed axon outgrowth after injury.

We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT) and the dorsal spinocerebellar tract (DSCT), respectively, in the sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by electrical stimulation of the contralateral lateral funiculus (coLF) and the ipsilateral LF (iLF) at lower thoracic levels. Most granule cells in sublobule C1 did not respond at all but part of the granule cell population displayed high-intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and Purkinje cell simple spikes responded to input from both LFs, although Golgi cells could be more selective. In addition, a small population of granule cells responded to input from both the coLF and the iLF. However, in these cases, similarities in the temporal topography and magnitude of the responses suggested that the same axons were stimulated from the two LFs, i.e., that the axons of individual spinocerebellar neurons could be present in both funiculi. This was also confirmed for a population of spinal neurons located within known locations of SBC-VSCT neurons and dorsal horn (dh) DSCT neurons. We conclude that bilateral spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and DSCT systems that provide the input can also be organized bilaterally. The implications for the traditional functional separation of VSCT and DSCT systems and the issue whether granule cells primarily integrate functionally similar information or not are discussed.

The dorsal spinocerebellar tract (DSCT) provides a major mossy fiber input to the spinocerebellum, which plays a significant role in the control of posture and locomotion. Recent work from our laboratory has provided evidence that DSCT neurons encode a global representation of hindlimb mechanics during passive limb movements. The framework that most successfully accounts for passive DSCT behavior is kinematics-based having the coordinates of the limb axis, limb-axis length and orientation. Here we examined the responses of DSCT neurons in decerebrate cats as they walked on a moving treadmill and compared them with the responses passive step-like movements of the hindlimb produced manually. We found that DSCT responses to active locomotion were quantitatively different from the responses to kinematically similar passive limb movements on the treadmill. The differences could not be simply accounted for by the difference in limb-axis kinematics in the two conditions, nor could they be accounted for by new or different response components. Instead, differences could be attributed to an increased relative prominence of specific response components occurring during the stance phase of active stepping, which may reflect a difference in the behavior of the sensory receptors and/or of the DSCT circuitry during active stepping. We propose from these results that DSCT neurons encode two global aspects of limb mechanics that are also important in controlling locomotion at the spinal level, namely the orientation angle of the limb axis and limb loading. Although limb-axis length seemed to be an independent predictor of DSCT activity during passive limb movements, we argue that it is not independent of limb loading, which is likely to be proportional to limb length under passive conditions.

Spinocerebellar systems are likely to be crucial for cerebellar hallmark functions such as coordination. However, in terms of cerebellar functional analyses, these are perhaps among the least explored systems. The aim of the present study is to achieve activation of a single component of the spinocerebellar systems and to explore to what extent it can influence the spike output of granule cells, Golgi cells, molecular layer (ML) interneurons (stellate and basket cells) and Purkinje cells (PCs). For this purpose, we took advantage of a unique arrangement discovered in neuroanatomical studies, in which the spinal border cell (SBC) component of the ventral spinocerebellar system was found to be the only spinocerebellar tract which ascends in the contralateral lateral funiculus (coLF) and have terminations in sublobulus C1 of the paramedian lobule in the posterior cerebellum. Using electrical stimulation of this tract, we find a subset of the cerebellar cortical neurons in this region to be moderately or powerfully activated. For example, some of our granule cells displayed high intensity responses whereas the majority of the granule cells displayed no response at all. The finding that more than half of the PCs were activated by stimulation of the SBC tract indicated that this system is capable of directly influencing cerebellar cortical output. The implications of these findings for the view of the integrative functions of the cerebellar cortex are discussed.

Neural circuits are organized into complex topographic maps. Although several neuroanatomical and genetic tools are available for studying circuit architecture, a limited number of methods exist for reliably revealing the global patterning of multiple topographic projections. Here we used wheat germ agglutinin (WGA) conjugated to Alexa 555 and 488 for dual color fluorescent mapping of parasagittal spinocerebellar topography in three dimensions. Using tissue section and wholemount imaging we show that WGA-Alexa tracers have three main characteristics that make them ideal tools for analyses of neural projection topography. First, the intense brightness of Alexa fluorophores allows multi-color imaging of patterned afferent projections in wholemount preparations. Second, WGA-Alexa tracers robustly label the entire trajectory of developing and adult projections. Third, long tracts such as the adult spinocerebellar tract can be traced in less than 6 h. Moreover, using WGA-Alexa tracers we resolved a level of complexity in the compartmentalized topography of the spinocerebellar projection map that has never before been appreciated. In summary, we introduce versatile tracers for rapidly labeling multiple topographic projections in three dimensions and uncover wiring complexities in the spinocerebellar map.

Spinocerebellar (SC) neurons in the lumbosacral enlargement (LSE) give rise mainly to crossed fibers and generally terminate in parasagittal bands in the granular layer of the chicken cerebellar cortex. However, parasagittal bands for mossy fiber terminals have not always been clear in some cerebellar folia. The present study aimed at (1) observing the course in the spinal cord of the spinocerebellar tracts (SCTs), (2) confirming whether SC fibers originating from the unilateral LSE terminate in parasagittal bands, and (3) elucidating the relationship between the ventral and lateral funicular parts of the SCTs in the cervical enlargement (CE) using anterograde and retrograde labeling methods. The SCTs were located in the medial part of the ventral funiculi in spinal segment (SS) 27, the full width of the ventral funiculi in SS 22, the lateral and ventral funiculi in SS 14 and in the lateral funiculi from SS 10 rostralward. Projection areas in the cerebellar cortex of SC fibers were studied following unilateral injections of WGA-HRP into the LSE. As a result, SC fibers from the LSE terminated bilaterally in parasagittal bands of folia II–VI and IXc. Labeled terminals in the injected side were similar in number to those in the other side in folia II–IV and IXc and more than those in the other side in folia V and VI. Following ablation of the left (contralateral) lateral funiculus of the CE, the same tracer was injected into the right (ipsilateral) LSE or into the anterior or posterior cerebellar lobe. As a result, anterogradely labeled SC fibers passing through the ventral funiculus in the CE mainly terminated in the contralateral cerebellar cortex in folia II, III and IV, and in the ipsilateral cerebellar cortex in folia V, VI and IX. Following ablation of the unilateral lateral funiculus, retrogradely labeled neurons in the contralateral LSE were found in all SC neuron groups showing marked reduction in number. Thus, the ventral and lateral funicular parts of the SCTs in the CE were not pathways for specific SC neuron groups but different in projection areas.

Study designProspective case-control study.ObjectivesWe investigated the use of the magnetization transfer saturation (MTsat) technique to assess the structural integrity of the spinal cord tracts in individuals with clinically significant degenerative cervical myelopathy (DCM) and associated disability.SettingNovosibirsk Neurosurgery Centre, Russia.MethodsA total of 53 individuals diagnosed with DCM and 41 patients with cervical radiculopathy underwent high-resolution MRI of the cervical spinal cord via the magnetization transfer technique. The MRI data were processed using the Spinal Cord Toolbox (v5.5), with MTsat values determined for each spinal tract and compared between the two groups. Furthermore, associations between MTsat values and the clinical disability rates of patients were investigated.ResultsA significant decrease in the MTsat of the ventral spinocerebellar tract was observed in the DCM group compared to the control group (adjusted p < 0.001). There was a trend towards lower MTsat values in the rubrospinal tract in the DCM group (adjusted p = 0.08). Additionally, a decrease in MTsat values in the lateral funiculi of the spinal cord was found in patients with DCM (adjusted p < 0.01). Furthermore, a trend toward a positive correlation was observed between the JOA score and the MTsat values within the ventral spinocerebellar tract (R = 0.33, adjusted p = 0.051).ConclusionsThe findings of our study indicate that demyelination in patients with DCM affects mainly the ventral spinocerebellar and rubrospinal tracts, and the extent of changes in the ventral spinocerebellar tract is related to the severity of the condition.

Purpose Degenerative cervical myelopathy (DCM) is a common cause of spinal cord dysfunction. In this study, we explored the potential of magnetization transfer ratio (MTR) for evaluating the structural integrity of spinal cord tracts in patients with clinically significant DCM. Methods Fifty-three patients with DCM and 41 patients with cervical radiculopathy were evaluated using high-resolution cervical spinal cord magnetic resonance imaging (MRI), which included the magnetization transfer technique. MRI data were analyzed with the Spinal Cord Toolbox (v5.5); MTR values in each spinal tract were calculated and compared between groups after correction for patient age and sex. Correlations between MTR values and patients’ clinical disability rate were also evaluated. Results A statistically significant reduction in the average MTR of the spinal cord white matter, as well as the MTR of the ventral columns and lateral funiculi, was revealed in the DCM group (adjusted p  < 0.01 for all comparisons). Furthermore, reductions in MTR values in the fasciculus cuneatus, spinocerebellar, rubrospinal, and reticulospinal tracts were found in patients with DCM (adjusted p  < 0.01 for all comparisons). Positive correlations between the JOA score and the MTR within the ventral columns of the spinal cord ( R  = 0.38, adjusted p  < 0.05) and the ventral spinocerebellar tract ( R  = 0.41, adjusted p  < 0.05) were revealed. Conclusion The findings of our study indicate that demyelination in patients with DCM primarily affects the spinal tracts of the extrapyramidal system, and the extent of these changes is related to the severity of the condition.