In this application we have one Specific Aim: To test a new model of saccade generation by the nigro-colliculus pathway by determining the influence of the inhibitory inputs from the substantia nigra pars reticulata (nigra) on identified neuronal cell types within the superior colliculus. To achieve this aim we propose two experiments using the in vitro rodent model. Each of these experiments will be performed on both projection neurons and GAD 67 GFP labeled interneurons within both the intermediate (premotor) layers and the superficial (visual) layers of the colliculus. We shall, 1) introduce hyperpolarizing current into collicular neurons to assess expression of Ih, the hyperpolarization activated cation current and use hyperpolarizing voltage steps under voltage clamp to test for Ih in collicular neurons. 2) Introduce realistic spike trains into the nigra and record from neurons in the colliculus to assess whether nigral activity invokes Ih leading to bursting in superior colliculus neurons. The work proposed here may change the current dogma regarding the role of the nigro-collicular pathway in eye movement initiation by showing that its role is active rather than a passive gating of cortical afferents. The results therefore, may provide a new understanding of how eye movement symptoms occurring in neurological and neuropsychiatric diseases involving the basal ganglia such as Parkinson's disease, Huntington's disease, Tourette syndrome, attention deficit disorder, obsessive compulsive disorder and schizophrenia arise.

Public Health Relevance

The goal of this application is to test a long-held hypothesis of basal ganglia function based on work performed in the oculomotor system. The work proposed here has the potential to change the current dogma regarding the role of the basal ganglia in eye movements by showing that its role is active rather than a passive gating of cortical afferents. The results therefore, may provide a new understanding of how eye movement symptoms occurring in neurological and neuropsychiatric diseases involving the basal ganglia such as Parkinson's disease, Huntington's disease, Tourette syndrome, attention deficit disorder, obsessive compulsive disorder and schizophrenia arise.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EY024153-01
Application #
8635227
Study Section
Special Emphasis Panel (ZRG1-IFCN-Q (02))
Program Officer
Araj, Houmam H
Project Start
2013-12-01
Project End
2015-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
1
Fiscal Year
2014
Total Cost
$198,010
Indirect Cost
$69,432
Name
University of California Los Angeles
Department
None
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095