In the neuroimaging literature, there is a large gap in knowledge regarding the relationship between blood oxygen level dependent signals (BOLD) that are measured and neuronal inhibition. The circuits in the basal ganglia that control the suppression and release of saccadic eye movements provide a unique opportunity to fill this gap in knowledge. We propose to study BOLD signals in response to activation of an inhibitory circuit involved in eye movement control. We will insert genes encoding the light-activated ion channel, ChR2 into an output nucleus of the basal ganglia causing them to express ChR2. A light source provided to the channel- expressing neurons will open ion channels and cause neuronal depolarization of inhibitory neurons. BOLD signals will be measured. We have one Specific Aim: to determine BOLD signals in response to activation of an inhibitory neural circuit involved in eye movement control. We will perform three experiments to achieve this aim. 1) Using the neuron-specific promoter CAG, we will express ChR2 in neurons of the substantia nigra pars reticulata (nigra) and measure BOLD responses to light activation using fMRI;2) using inhibitory neuron-specific promoters (PV and GAD67) we will express ChR2 in inhibitory nigral neurons and measure BOLD signals in response to light activation using fMRI;3) we will record the electrical activity (LFPs) in the super colliculus and the thalamus (targets of nigral inhibition) in response to light activation to compare BOLD responses to electrical responses. The results of these experiments will uncover critical mechanisms of neural processing of inhibition and how this fundamental neuronal activity appears in BOLD signals.

Public Health Relevance

How blood oxygen level dependent signals (BOLD) measured with functional magnetic resonance imaging (fMRI) correspond to the electrical currency of brain activity is under studied. The inhibitory pathway through the basal ganglia that controls eye movements provides a unique opportunity to discover how BOLD signals related to neuronal inhibition. The results of these experiments will uncover how this fundamental neuronal activity appears in BOLD signals.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EY024516-01A1
Application #
8776030
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Araj, Houmam H
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
None
Type
Overall Medical
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90095