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INVOLVEMENT OF THE CEREBELLUM IN SKILLED FORELIMB FUNCTION BEFORE AND AFTER CERVICAL LESIONS
Eneanya, Chidubem
Eneanya, Chidubem
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2025-08
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Biomedical Sciences
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https://doi.org/10.34944/yfj7-2s64
Abstract
Goal-directed reaching movements are extremely accurate in which the location, placement, and speed of the limbs is specific from trial to trial. After a cervical spinal cord injury (SCI), there is a loss of both descending motor commands and ascending sensory information, which causes a disruption of forelimb motor responses. The re- introduction of function requires rehabilitation and descending motor information. Functional recovery also requires the precision of movement which involves sensory feedback for error correction and increased synchronization of motor responses. As SCI eradicates conscious sensory information, the contribution of unconscious proprioceptive information from the cerebellum in error correction becomes exceedingly vital. Therefore, we hypothesize that, sensory input to and efferent output from the cerebellum are responsible for feedback modulation of forelimb function before and after cervical spinal cord lesions. Input is mediated by the external cuneate nucleus (ECN) and the central cervical nucleus (CeCv), which send unconscious proprioceptive information to the deep cerebellar nuclei (DCN), within the cerebellum. The DCN provide error correction and transmits this efferent information to the brainstem and spinal cord motor nuclei.Using a multi-level genetic methodology, we will assess the significance of the ECN and CeCv in facilitating forelimb coordination by expressing a CRE-dependent hM4Di (inhibitory DREADDs) in these specific regions. When a CRE-dependent inhibitory DREADDs was expressed in the ECN, in combination with CNO, we observed a disruption in the single pellet reaching and grasping behavioral model, in two pre- lesioned cohorts, unilaterally and bilaterally. When this same method was applied to the grooming behavioral model, we also reached statistical significance. Previous research was unable to substantiate the termination of the CeCv, so we were able to uncover that the CeCv, mainly, terminates into the medial cerebellar nuclei (MCN). This data demonstrates that the sensory input from the ECN and CeCv is involved and critical for skilled forelimb function. When we mapped the DCN efferent output, we observed that the rubrospinal tract, nucleus gigantocellularis reticularis, and lamina 7 of the spinal gray were strongly labeled. All these areas are associated with the forelimb function, suggesting their imperative role in forelimb function.
In conclusion, we have demonstrated the significance of the sensory input and the efferent output from the cerebellum in forelimb function. We have highlighted a potential alternative therapeutic to the thousands of people leaving with SCIs. These studies will emphasize the vital roles of the sensory input into the cerebellum as well as efferent output into the brainstem and spinal cord motor nuclei and its influence on motor control for recovery after spinal cord injuries. This data will shed light on the association of essential indirect motor pathways with the function and recovery of skilled forelimb patterning and provide an avenue to new studies promoting arm and hand recovery in more severe clinically relevant injury models.
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