Networks of rhythmically active neurons in the spinal cord are responsible for producing locomotor movements. In developing vertebrates, ventral spinal cord can be sub-divided into five zones, four of which are responsible for producing the interneurons that drive rhythmic motoneuron activity (V0-V3). Critically, interneurons that emerge from these zones are labeled by the same transcription factors and have similar morphologies and functions in different vertebrates. This has made it even easier to compare features of circuit organization in simpler model systems, like fishes and frogs, to more complex ones, like chicks and mice. What is unclear, however, is how only four progenitor zones can yield the diverse array of functionally distinct interneurons that are known to exist. Our plan is to explore the contribution of development to the functional elaboration of spinal circuitry, by studying a genetically identified population of spinal interneurons in zebrafish. Our work suggests that interneurons labeled by the transcription factor alx in zebrafish are not functionally identical and contribute to different speeds of movement. However, it is not clear how differences in the morphology, connectivity and the excitability of alx interneurons may be related to their function and whether developmental programs shape these features. The remarkable conservation of developmental mechanisms leads us to think that the patterns we find will be present broadly among vertebrates, including mammals. By doing so, we hope to better explain and treat disorders that affect the speed and coordination of movements, like Parkinson's disease or spinal injury.

Public Health Relevance

Networks of neurons in the spinal cord generate movements, but we understand very little about their organization. We will investigate the contribution of development to the functional diversification of spinal networks using zebrafish as a model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS067299-03
Application #
8204704
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Chen, Daofen
Project Start
2010-03-01
Project End
2014-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
3
Fiscal Year
2012
Total Cost
$306,650
Indirect Cost
$92,275
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
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
Bagnall, Martha W; McLean, David L (2014) Modular organization of axial microcircuits in zebrafish. Science 343:197-200
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
Menelaou, Evdokia; VanDunk, Cassandra; McLean, David L (2014) Differences in the morphology of spinal V2a neurons reflect their recruitment order during swimming in larval zebrafish. J Comp Neurol 522:1232-48
Wang, Wei-Chun; McLean, David L (2014) Selective responses to tonic descending commands by temporal summation in a spinal motor pool. Neuron 83:708-21
Patterson, Bradley W; Abraham, Aliza O; MacIver, Malcolm A et al. (2013) Visually guided gradation of prey capture movements in larval zebrafish. J Exp Biol 216:3071-83
McLean, David L (2013) Optogenetics: illuminating sources of locomotor drive. Curr Biol 23:R441-3
Menelaou, Evdokia; McLean, David L (2013) Speed control: spinal interneurons with crossed purposes. Curr Biol 23:R716-8
Menelaou, Evdokia; McLean, David L (2012) A gradient in endogenous rhythmicity and oscillatory drive matches recruitment order in an axial motor pool. J Neurosci 32:10925-39

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