Project 1. Specification and Synaptogenesis of Excitatory Locomotor NeuronsExcitatory interneurons in the ventral spinal cord play important roles in the circuits that control voluntarymovements. Very little is known about how these cell types are specified and how they are assembled intofunctional circuits. In this proposal we will define the genetic program that specifies the V3 class ofglutamtergic inteneurons by focusing on the function of two known bHLH transcription factors, Mashl andNgn3. We will examine the function of V3 interneurons in the locomotor behaviors by genetically ablating orsilencing them and assaying motor outputs. We will use a novel genetic assay system that we havedeveloped to look at synaptic connections from V2 and V3 neurons onto other locomotor circuit neurons,including motor neurons and Renshaw cells. We will examine the development of these connections, andask whether activity plays are role in generating specific patterns of connectivity in the spinal cord withrespect to these glutamatergic interneuron synapses. We will also assess the role that the transcriptionfactors Sim1 and Uncx4.1 play in V3 interneuron axon guidance and synapse formation. Finally, we willaddress the role that Eph-signaling plays in controlling the axon morphology and connectivity of excitatoryneurons such as V3 neurons. These studies will begin to map connections between identified locomotorneurons and determine the mechanisms that control their assembly. As such, this research will providefundamental insights into the development and organization of circuits in the spinal cord that controllocomotion, and will lay the ground work for strategies to treat spinal cord injury and degeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
2P01NS031249-14A1
Application #
7186070
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2007-06-01
Budget End
2008-03-31
Support Year
14
Fiscal Year
2007
Total Cost
$339,675
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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