RP 1: Modeling Forelimb Motor Circuit Organization and Function

Information

  • Research Project
  • 10226040
  • ApplicationId
    10226040
  • Core Project Number
    U19NS112959
  • Full Project Number
    5U19NS112959-03
  • Serial Number
    112959
  • FOA Number
    RFA-NS-19-003
  • Sub Project Id
    7296
  • Project Start Date
    9/15/2019 - 5 years ago
  • Project End Date
    6/30/2024 - 6 months ago
  • Program Officer Name
  • Budget Start Date
    7/1/2021 - 3 years ago
  • Budget End Date
    6/30/2022 - 2 years ago
  • Fiscal Year
    2021
  • Support Year
    03
  • Suffix
  • Award Notice Date
    9/9/2021 - 3 years ago

RP 1: Modeling Forelimb Motor Circuit Organization and Function

Project Summary: Project 1 ? Modeling Forelimb Motor Circuit Organization and Function This Research Project addresses the dynamics of motor circuits in the cervical spinal cord. Aims in this project will analyze how cervical spinal networks coordinate forelimb movement during rhythmic and non-rhythmic activity. The model will include neuronal elements (excitatory and inhibitory pre-motor neurons and antagonist pools of motor neurons), antagonist pairs of muscles, and mechanical components of the limb. Theoretical and computational techniques will be used to describe how these elements interact, including possible responses to descending brain commands, to generate forelimb activities such as isometric and isotonic movements. The first goal will be to compute how cervical spinal motor neurons fire in response to inputs (based on slice electrophysiology experiments, Projects 2 and 3), and how their firing is converted to muscle force (based on EMG recordings, Project 4). A second goal will be to analyze circuit configurations that achieve maximum control in order and predict new functional cell types that may be present in the spinal cord. Network models composed of motor and pre-motor neurons will then be constructed, defining the patterns of network firing and bursting of antagonistic motor pools, corresponding to elbow and wrist movements and static states. The model will be constrained by connectivity data (Project 2), and informed by theoretical analyses of optimal circuit configurations. Finally, a mechanical model of the limb will be connected to the neuronal model to generate a coherent picture of the transformation from descending input to the cervical spinal cord to limb movements. The dynamical responses of the model will be compared with the behavioral and in vivo electrophysiological data collected in Project 4. Overall, the theoretical analyses performed here, together with experimental investigations from Projects 2-4, will help inform general principles concerning how multiple neuronal types coordinate their response properties to achieve robust control of multiple dynamical variables.

IC Name
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
  • Activity
    U19
  • Administering IC
    NS
  • Application Type
    5
  • Direct Cost Amount
    171685
  • Indirect Cost Amount
    109739
  • Total Cost
  • Sub Project Total Cost
    281424
  • ARRA Funded
    False
  • CFDA Code
  • Ed Inst. Type
  • Funding ICs
    NINDS:281424\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZNS1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    SALK INSTITUTE FOR BIOLOGICAL STUDIES
  • Organization Department
  • Organization DUNS
    078731668
  • Organization City
    La Jolla
  • Organization State
    CA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    920371002
  • Organization District
    UNITED STATES