The focus of this proposal is to examine the functional and structural organization of a vertebrate spinal network responsible for generating coordinated locomotor activity. To construct a more thorough understanding of network organization it is important to address fundamental issues including the identification of key neuronal components and the characterization of their cellular and synaptic connectivity properties, which help to generate or support the motor output. This study is designed to test specific hypotheses in an attempt to progress our understanding of the organization of the spinal network that produces swimming in larval zebrafish.
The specific aims are: 1) To characterize the morphological and neurotransmitter properties of the interneuronal populations marked by Hb9 in the larval zebrafish spinal cord, 2) To test the hypothesis that an identified Hb9 spinal interneuron population or populations participate in driving the locomotor rhythm, and 3) To test the hypothesis that intrinsic membrane properties contribute to the generation of locomotor activity. A combination of neurogenetic, optical imaging and conventional electrophysiological techniques will be used to determine the functional roles specific, identified spinal interneurons play in generating the locomotor drive underlying swimming behavior in zebrafish. Ultimately, the approach outlined in this project will provide a fundamental understanding of the organization of the neural network that generates vertebrate locomotion, which can be used to inform clinical and procedural strategies to treat individuals with spinal cord injuries.

Public Health Relevance

In vertebrates, the neural network that drives locomotion is composed of a set of interconnected interneurons located in the spinal cord. Our goal is to gain a fundamental understanding of how the vertebrate spinal networks are organized to generate a coordinated pattern of motor activity, which will provide elemental information central to the development of novel concepts and potential clinical management of spinal cord injuries.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Sensorimotor Integration Study Section (SMI)
Program Officer
Chen, Daofen
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University of Minnesota Twin Cities
Schools of Medicine
United States
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Montgomery, Jacob E; Wahlstrom-Helgren, Sarah; Wiggin, Timothy D et al. (2018) Intraspinal serotonergic signaling suppresses locomotor activity in larval zebrafish. Dev Neurobiol :
Montgomery, Jacob E; Wiggin, Timothy D; Rivera-Perez, Luis M et al. (2016) Intraspinal serotonergic neurons consist of two, temporally distinct populations in developing zebrafish. Dev Neurobiol 76:673-87
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Ingebretson, Justin J; Masino, Mark A (2013) Quantification of locomotor activity in larval zebrafish: considerations for the design of high-throughput behavioral studies. Front Neural Circuits 7:109
Wiggin, Timothy (2013) Motor unit properties and recruitment in the larval zebrafish. J Neurosci 33:853-4
Masino, Mark A; Abbinanti, Matthew D; Eian, John et al. (2012) TTX-resistant NMDA receptor-mediated membrane potential oscillations in neonatal mouse Hb9 interneurons. PLoS One 7:e47940
Lambert, Aaron M; Bonkowsky, Joshua L; Masino, Mark A (2012) The conserved dopaminergic diencephalospinal tract mediates vertebrate locomotor development in zebrafish larvae. J Neurosci 32:13488-500
Wiggin, Timothy D; Anderson, Tatiana M; Eian, John et al. (2012) Episodic swimming in the larval zebrafish is generated by a spatially distributed spinal network with modular functional organization. J Neurophysiol 108:925-34
Friedrich, Timo; Lambert, Aaron M; Masino, Mark A et al. (2012) Mutation of zebrafish dihydrolipoamide branched-chain transacylase E2 results in motor dysfunction and models maple syrup urine disease. Dis Model Mech 5:248-58

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