The overall goal of my research program is to understand the role of the basal ganglia (BG) and superior colliculus (SC) in saccadic eye movement choice and decision-making. In this application we are focused on extending our recent results from multiple neuron recordings in SC to simultaneous, multiple neuronal recordings of SC and a BG structure that has inputs to the SC, the substantia nigra pars reticulata (SNr). We have one Specific Aim;to reveal the coordinated activity of neurons within the SNr-SC pathway during saccade choice and decision-making. To achieve our aim we propose the following: We will implement a decision task in which the difficulty level of the saccade choice is manipulated explicitly and the probability of the saccade choice in conditions of sensory certainty and uncertainty is varied. We will record simultaneously from multiple neurons in the SNr and the SC during performance of this task. We will test the hypothesis the activity of SC and SNr neurons is modulated by choice difficulty and performance. We predict that harder choices and poorer performance will be associated with higher levels of SNr activity and lower levels of SC activity. We will implement our Bayesian inference model and incorporates measured noised correlations to elucidate the role of the SNr-SC pathway in saccade choice. We expect our results will build on the growing body of evidence implicating sensorimotor brain regions in neuronal processing related to choice and decision- making. The results will also provide critical and detailed information about the relationship of the SNr to the SC and how this pathway contributes to saccade choices. They will also provide the first evidence for a role of the SNr in perceptual decision-making. Finally, since eye movement abnormalities are a prominent symptom in a number of BG and cortico-BG diseases such as Parkinson's disease, Tourette Syndrome and obsessive compulsive disorder our results should provide important insights into the mechanisms of symptomology in many disease states.

Public Health Relevance

The experiments outlined in this proposal are designed to reveal insights into the role of the basal ganglia and superior colliculus in eye movement choice and perceptual decision-making. Because eye movement abnormalities are a prominent symptom in a number of basal ganglia and cortico-basal ganglia diseases such as Parkinson's disease, Tourette Syndrome and obsessive compulsive disorder, our results should provide important insights into the mechanisms of symptomology in many disease states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS065776-01A2
Application #
7991183
Study Section
Special Emphasis Panel (ZRG1-IFCN-L (02))
Program Officer
Gnadt, James W
Project Start
2010-05-01
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
1
Fiscal Year
2010
Total Cost
$212,838
Indirect Cost
Name
University of Wisconsin Madison
Department
Physiology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Mahamed, Safraaz; Garrison, Tiffany J; Shires, Joel et al. (2014) Stimulation of the substantia nigra influences the specification of memory-guided saccades. J Neurophysiol 111:804-16
Basso, M A; Sommer, M A (2011) Exploring the role of the substantia nigra pars reticulata in eye movements. Neuroscience 198:205-12
Shires, Joel; Joshi, Siddhartha; Basso, Michele A (2010) Shedding new light on the role of the basal ganglia-superior colliculus pathway in eye movements. Curr Opin Neurobiol 20:717-25