) The long-term goal of the proposed research is to understand the neural mechanisms underlying the control of motor output under normal and pathological conditions. We examine here how functional circuitry in the superior colliculus (SC), a bilateral midbrain structure known to be important for orienting behaviors, contributes to decisions about movements. The central hypothesis is that competition between spatial targets represented in the two SCs is mediated by commissural SC neurons that engage local inhibition. We test this hypothesis by recording and manipulating the activity of specific classes of neurons in freely-moving transgenic mice performing olfactory-cued spatial choice tasks.
Aim 1 will examine how the activity within one SC of excitatory and inhibitory SC neurons, examined in separate sets of mice, underlies spatial choice.
Aim 2 will examine how this activity, and the influence of inhibition on excitatory SC activity within the same SC, is modulated by competition between spatial targets represented by the two SCs.
Aim 3 will examine the role of commissural SC neurons in mediating this competition between spatial targets. If successful, the overall impact of our proposal will be the elucidation of how excitatory and inhibitory SC neurons interact ? within one SC and between the two SCs ? to mediate spatial choice, an important form of decision making. In addition to testing the specific hypotheses proposed here, the model we develop will make possible future research into how other genetically-defined networks of neurons contribute to decisions about movements. Ultimately, understanding normal motor control can contribute to improving therapies for movement disorders, such as Parkinson's disease.

Public Health Relevance

This proposal examines how activity of specific types of neurons contribute to making decisions about movements. Understanding this activity under normal conditions, and how it is altered under pathological conditions, can contribute to improving treatments for movement disorders like Parkinson's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS079518-09
Application #
10063568
Study Section
Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
Program Officer
David, Karen Kate
Project Start
2012-09-20
Project End
2022-11-30
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
9
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Physiology
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Thompson, John A; Costabile, Jamie D; Felsen, Gidon (2016) Mesencephalic representations of recent experience influence decision making. Elife 5:
Essig, Jaclyn; Felsen, Gidon (2016) Warning! Dopaminergic Modulation of the Superior Colliculus. Trends Neurosci 39:2-4
Lintz, Mario J; Felsen, Gidon (2016) Basal ganglia output reflects internally-specified movements. Elife 5:
Stubblefield, Elizabeth A; Thompson, John A; Felsen, Gidon (2015) Optogenetic cholinergic modulation of the mouse superior colliculus in vivo. J Neurophysiol 114:978-88
Wolf, Andrew B; Lintz, Mario J; Costabile, Jamie D et al. (2015) An integrative role for the superior colliculus in selecting targets for movements. J Neurophysiol 114:2118-31
Al-Juboori, Saif I; Dondzillo, Anna; Stubblefield, Elizabeth A et al. (2013) Light scattering properties vary across different regions of the adult mouse brain. PLoS One 8:e67626
Thompson, John A; Felsen, Gidon (2013) Activity in mouse pedunculopontine tegmental nucleus reflects action and outcome in a decision-making task. J Neurophysiol 110:2817-29
Stubblefield, Elizabeth A; Costabile, Jamie D; Felsen, Gidon (2013) Optogenetic investigation of the role of the superior colliculus in orienting movements. Behav Brain Res 255:55-63