Dopamine plays important roles in learning and motivation. It has been thought that dopamine neurons (DANs) signal reward prediction errors (RPEs) but this idea has been challenged by some recent findings. For one, some studies found that dopamine concentration in the ventral striatum slowly ramps up on the timescale of several seconds during goal-directed navigation, and it was proposed that these slow-timescale dopamine fluctuations may encode Value instead of RPEs. Because RPEs (as defined by temporal difference error in reinforcement learning theories) are approximately the temporal derivative of Value, these proposals are incompatible with the RPE hypothesis. As discussed in Project 1, a theory predicts that ramping dopamine can be explained by RPEs in certain conditions. This project (Project 3) will put this idea into experimental tests. A set of experimental tests will be developed using virtual reality in head-fixed mice (Aim 1). Specifically, RPE and Value accounts will be dissociated by teleporting the animal to a new location associated with a different Value, or by changing the speed of the scene movement.
Aim 2 will test the hypothesize that an explicit cue that indicates the proximity of reward is sufficient to induce a dopamine ramp in non-navigational contexts. Furthermore, by manipulating stimulus parameters, Aim 2 also aims at determining under what task conditions dopamine ramps or not.
Aim 3 will experimentally manipulate DAN activity, and examine the function of slowly- fluctuating dopamine signals in the regulation of the activity of spiny projection neurons in the striatum and behaviors in goal-directed navigation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19NS113201-02
Application #
9993582
Study Section
Special Emphasis Panel (ZNS1)
Project Start
2019-08-15
Project End
2024-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Type
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115