Movements underlie all forms of vertebrate behavior and are driven by excitatory and inhibitory circuitry within the spinal cord. During locomotion, these networks generate rhythmic commands to motor neurons innervating muscles in the limbs and trunk. In all vertebrates, the motor neurons and their target musculature (motor units) are organized as functional synergists and antagonists. While excitatory circuits ensure the coordinated activation of functionally synergistic motor units, inhibitory circuits maintain the alternation of functionally antagonistic ones. As movements are generated with greater intensity, larger motor units that can exert greater force are recruited into the active pool in an orderly fashion that matches features related to their size, excitability and target musculature. However, regardless of intensity of locomotion, antagonistic motor units are typically activated in alternation. Despite decades of work studying the spinal inhibitory circuitry responsible for left-right or flexor-extensor alternation, relatively little is known about how inhibition is organized o ensure the appropriate activation of motor units of differing sizes during variations in movement speed or strength. Our goal is to determine the existence of systematic patterns of reciprocal inhibition that help coordinate the recruitment patterns of spinal motor neurons during locomotion using zebrafish as a model system. We will test the hypothesis that the strength of inhibitory synaptic connections arises in an orderly fashion during development and is mapped according to speed within motor neurons, such that inhibition at faster speeds arrives early and more proximally, while inhibition at slower speeds arrives later and more distally. The patterns we reveal here will provide critical mechanistic insight into the normal functional integration of inhibition and motor neuron excitability, disruptions of which underlie numerous motor diseases and disorders.

Public Health Relevance

Movements can be graded in speed and strength, but it is unclear how spinal networks accomplish this task. Our goal is to determine the existence of systematic patterns of reciprocal inhibition that help coordinate the recruitment patterns of spina motor neurons during locomotion using zebrafish as a model system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS067299-10
Application #
9626956
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Chen, Daofen
Project Start
2010-03-01
Project End
2020-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
10
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
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McLean, David L; Dougherty, Kimberly J (2015) Peeling back the layers of locomotor control in the spinal cord. Curr Opin Neurobiol 33:63-70
Kishore, Sandeep; McLean, David L (2015) Neuromodulation: letting sources of spinal dopamine speak for themselves. Curr Biol 25:R146-8
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Kishore, Sandeep; Bagnall, Martha W; McLean, David L (2014) Systematic shifts in the balance of excitation and inhibition coordinate the activity of axial motor pools at different speeds of locomotion. J Neurosci 34:14046-54
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