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Project

Targeting propriospinal neurons to improve breathing following injury

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Propriospinal neurons are critical mediators of recovery from spinal cord injury. Enhancing the function or plasticity of propriospinal pathways has significant therapeutic potential but has thus far been limited by a lack of knowledge of which neurons are critical for recovery and what molecules are relevant targets. Our previous findings and preliminary data indicate that increasing the excitability of V2a neurons can enhance respiratory muscle function by 1) activating crossed phrenic pathways spared by injury and 2) increasing the activity of extra-diaphragmatic respiratory muscles. Additional respiratory muscles (ARMs) stabilize the chest or abdomen and augment diaphragm function. ARM dysfunction in spinal cord injury patients can lead to paradoxical breathing, impaired cough, and respiratory infections. We hypothesize that molecules that activate G-protein coupled signaling pathways in V2a neurons and/or promote increased connectivity between V2a neurons and respiratory motor neurons will improve recovery of respiratory function following spinal cord injury. Aim 1 will identify G-protein coupled receptors and downstream signaling components expressed in V2a neurons acutely following injury using single nuclei RNA sequencing analysis. Aim 2 will identify molecules/ pathways whose expression is altered in spinal V2a neurons during recovery from injury that could promote increased connectivity to respiratory muscles. Aim 3 will identify the location (relative to injury) of V2a neurons capable of promoting respiratory muscle function following a C2 hemisection injury using targeted expression of Gq-DREADD to alter V2a neuron activity and chronic electromyography recordings to assess respiratory muscle function prior to and during recovery from injury. Together, these studies will identify molecular targets in V2a neurons best suited to promote respiratory motor function, prevent ventilator dependence, and reduce respiratory infections in patients with 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

    Neurosciences

  • RCDC

    Lung

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • HRCS HC

    Neurological

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science