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Project

Viral constructs for the reversible inactivation of spinal interneurons

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
This project will use combinatorial viral vector constructs to study the role of commissural interneurons in the left-right coordination of the locomotor cycle in the adult mammalian spinal cord. Studies in knock-out mice have identified genetically defined populations of commissural interneurons (V0 interneurons) whose ablations lead to disruption of the left-right cycle in in-vitro spinal cord preparations, and an hopping locomotion phenotype in mice. Studies in neonatal rats in-vitro spinal preparations have confirmed that the left-right alternating circuitry is based on commissural interneurons with excitatory and inhibitory connections projecting contralaterally from the flexor dominant L2 spinal segment to the extensor dominant L5 spinal segment. At the moment, little is known about the organization in the adult spinal cord, and about the amount of redundancy in the projections between the left and right hemicords. Our combinatorial viral vector approach will allow us to target interneurons at specific spinal segments and test hypotheses about the rostrocaudal organization of the left-right coordination of the locomotor cycle. We intend to test the constructs in cats. Testing in the adult spinal cat will allow us to conduct detailed kinematics and muscle activation studies of the disruption brought upon by the excitation or inactivation of lamina VIII commissural interneuronal populations that are hypothesized to be the cat analogue of the V0 population in the rat. In addition, the use of the cat model will allow us to measure interneuronal population activity during locomotor behavior in the pre- and post-activity modulation conditions. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Genetics

  • RCDC

    Neurodegenerative

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science