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Project

Plasticity Of Reticulospinal Pathways Following Spinal Cord Injury

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Following incomplete spinal cord injury (SCI) at the thoracic level, animals exhibit postural adjustments in their contralesional hindlimb (opposite to the injury) to compensate for hindpaw dragging in their ipsilesional hindlimb (on the side of the injury). While postural adjustments in the contralesional limb persist over time, the ipsilesional limb recovers locomotion within a few weeks. These respective changes are presumably supported by a reorganization of spared neuronal pathways at the spinal level, through propriospinal neurons, and/or at the brain level, through supraspinal neurons. Whereas it is well established that the medullary reticular formation relays cortical and mesencephalic inputs important to locomotion and postural adjustments, less is known about the identity, physiological properties, network connectivity, and plasticity of these reticulospinal pathways. Indeed, some brainstem nuclei are important to locomotion in normal settings, while others only emerge over time to promote functional locomotor recovery after SCI. Given their position between supraspinal locomotor centers and the diversity of nuclei throughout the medullary reticular formation, we hypothesize that some reticulospinal neurons of the medullary reticular formation will contribute to postural adjustments of the contralesional hindlimb, whereas others will contribute to functional locomotor recovery of the ipsilesional hindlimb after SCI. Combining conditional genetics in the mouse, we will tag glutamatergic reticulospinal (GluT+RS) neurons according to their spinal projections. Using these mice, we will investigate their physiological properties, firing pattern, and synaptic efficacy to motor and locomotor recovery after SCI. The following aims will be addressed: - Specific Aim #1: Using whole-cell patch-clamp recordings, we will evaluate changes in intrinsic and extrinsic physiological properties of GluT+RS neurons. - Specific Aim #2: Combining multi-unit recordings and optogenetic tools, we will monitor the firing pattern and motor efficacy of GluT+RS neurons after SCI. - Specific Aim #3: We will investigate the necessity of GluT+RS neurons to postural adjustments and locomotor recovery after SCI. By the completion of this 2-year research project, we will have identified and characterized the intrinsic, synaptic, and functional changes of GluT+RS pathways important to functional motor recovery after SCI. Given the clinical potential of targeting these reticulospinal pathways by cortical stimulation through trans-cranial stimulation of the motor cortex or deep brain stimulation of the mesencephalic locomotor region, it is becoming crucial to study their functional contribution after SCI. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Neurosciences

  • RCDC

    Rehabilitation

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • RCDC

    Physical Rehabilitation

  • HRCS HC

    Neurological

  • HRCS RAC

    1.1 Normal biological development and functioning

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science