Dopamine (DA) has been involved in the production of locomotor behaviors throughout evolutionary time. Multiple DA populations in the brain and the spinal cord have been implicated in this process, however several DA populations remain unstudied. Here, we investigate a population of hypothalamic DA neurons that we have recently shown to be critically involved in the production of locomotor behaviors in zebrafish. These neurons are genetically defined by expression of tyrosine hydroxylase-2 (th2). We have shown that ablation of these neurons grossly reduces locomotion and that optogenetic activation increases it. However, the precise nature of the behaviors that are affected by the th2+ neurons is not well understood. To understand how these neurons modulate locomotor behavior, we must know where they send their projections, how their activity modulates those downstream targets, and the precise nature of the behaviors that result from that modulation.
The first aim of the proposed work is to identify downstream targets both anatomically and functionally..
The second aim i s to precisely identify locomotor patterns regulated by th2+ neurons. This will provide a detailed understanding of the output of the network. These experiments will identify previously unknown mechanisms by which hypothalamic DA neurons modulate locomotor behaviors.

Public Health Relevance

Dysfunction of dopamine neurons is common to many neurological disorders, including Parkinson?s, schizophrenia, and Tourette?s syndrome. To understand these diseases, we must understand how the normal activities of dopaminergic neurons shape circuit activity and behavior. This work will characterize the network mechanisms by which a population of hypothalamic dopamine neurons influences sensorimotor processing in larval zebrafish.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS100412-03
Application #
9614341
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Riddle, Robert D
Project Start
2016-12-07
Project End
2019-12-06
Budget Start
2018-12-07
Budget End
2019-12-06
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Utah
Department
Neurosciences
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112