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Project

Activating dI3 interneurons to promote recovery of locomotor function

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Spinal cord injury leads to loss of motor and sensory function due to disrupted connections between the brain and the spinal cord. Experimental studies in animal models suggest that the isolated spinal cord can regain lost motor function. Recent clinical studies have shown that rehabilitative strategies centered around locomotor training enable some recovery of lost locomotor function. Dramatic improvements in the recovery of lost locomotor function following spinal cord injury could be made if we understand which spinal neurons drive recovery during rehabilitation. My work has identified a population of spinal neurons that play an important role in recovery following spinal cord injury. Eliminating these spinal neurons, named dI3 interneurons, compromises the ability of mice to recover from spinal cord injury through treadmill training. Therefore, my work identifies a key neuron in the process of recovery.

We propose to study whether selectively increasing the activity of dI3 interneurons could improve the recovery of locomotor function. To do this, we will use novel technology that enable select populations of neurons to be inactivated or activated through orally administered compounds in a mouse model of spinal cord injury. We will first determine the mechanisms by which dI3 interneurons promote locomotor recovery. Afterwards, we will use light stimulation to demonstrate that activating dI3 interneurons can activate spinal locomotor networks. Finally, we will determine whether activating dI3 interneurons using oral administration of a designer drug is sufficient to promote recovery or to enhance locomotor recovery when combined with locomotor training on a treadmill. This work will be an important step in the development of new therapeutic strategies for prolonged improvement of locomotor function following spinal cord injury.

(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

    Bioengineering

  • 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