Impaired motor skill and habit-learning deficits have often been observed in Parkinson's disease patients well before the onset of clinically identifiable movement disorders, indicating that dopamine plays an important role in procedural habit learning. However, activities of midbrain dopaminergic (DA) neurons are regulated by cortical and subcortical signals among which glutamatergic afferents provide excitatory inputs. In this application, we set out to genetically examine the role of the NMDA receptor in the dopamine neural circuitry, namely, the ventral tegmental area and substantia nigra pars compacta as well as in the striatum in habit learning. We will generate a series of region-specific and inducible NMDA receptor knockout mouse lines to define the temporal stages during which habit is formed and stored. We will further combine conditional knockout mice with optogentic and neural ensemble recording techniques to systematically investigate the roles of the DA neuron NMDA receptor in neural dynamical patterns associated with habit learning. We believe that this integrated approach may provide us not only with important insight into the molecular and temporal mechanisms of habit learning, but also with potential novel therapeutic strategies for preventing and treating Parkinson's disease.

Public Health Relevance

Decoding the upstream pathways regulating dopamine is crucial for understanding habit learning. This application will apply a set of molecular genetics and neural ensemble recording techniques to investigate the NMDA receptor-mediated molecular and temporal mechanisms of habit formation in the dopaminergic neural circuitry in the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS079774-03
Application #
8663328
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Babcock, Debra J
Project Start
2012-09-01
Project End
2017-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$413,975
Indirect Cost
$137,992
Name
Georgia Regents University
Department
Neurology
Type
Schools of Medicine
DUNS #
966668691
City
Augusta
State
GA
Country
United States
Zip Code
30912