The long-term goal of these investigations is to understand the circuit plasticity underlying the association of an arbitrary sensory stimulus with an arbitrary action. Understanding this circuitry is likely to have an impact on the diagnosis and treatment of clinically important central neuropathologies, including Huntington's disease, Parkinson's disease, addiction, schizophrenia, and obsessive compulsive disorder. The central goal of this proposal is to test the hypothesis that differential plasticity at the cortical projection to two different neuronal subpopulations in the striatum underlie the acquisition of a sensorimotor discrimination behavior. We use mice as a model system because they allow sophisticated interrogation of genetically defined subpopulations of neurons.
In Aim 1 we use in vitro electrophysiological methods in acute brain slices to study the strength of corticostriatal synapses in animals trained on a simple task associating sounds with a left or right choice.
In Aim 2 we will use the same methods to study animals trained on a task requiring greater behavioral flexibility. Finally in Aim 3, we test whether association of the sound and action leads to differential changes at the two subpopulations of striatal neurons. These studies will provide insight into how animals acquire arbitrary associations, and provide a foundation for further study of role of these neurons in normal function and disease, facilitating the development of treatments for psychiatric and neurological diseases.

Public Health Relevance

This proposal will test compare the function of two classes of neurons in the striatum, a structure implicated in the etiology of clinically important neuropathologies, including Huntington's disease, Parkinson's disease and addiction. If successful, our studies will lead to improved strategies for diagnosing and treating these and related disorders.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01NS088649-01
Application #
8765972
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Gnadt, James W
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724