Mesolimbic dopamine, along with its ventral striatal targets, plays a major role in Pavlovian reward learning. Pavlovian reward learning processes underlie many aspects of drug seeking behavior and play a critical role in drug relapse. Instrumental learning processes also form a fundamental element of drug seeking behavior, and may depend on nigrostriatal dopamine innervation of dorsal striatum. Here we seek to understand how mesolimbic and nigrostriatal dopamine action within striatal targets mediates select components of reward-seeking behavior, and to test whether interactions between these systems contribute to normal and pathological reward-seeking behavior. We focus on dopamine because both natural and drug rewards activate dopamine neurons, and, as confirmed in our recent findings, dopamine neuron activation, when substituted for reward, drives specific forms of associative learning implicated in addictive behavior. Here, using the Th:Cre transgenic rat to limit channelrhodopsin expression to dopamine neurons, we take advantage of the ability to selectively activate mesolimbic dopamine neurons to better understand their impact on behavior, neural activity, and integration of ventral and dorsal striatal systems. We test whether mesolimbic dopamine neuron reward-related activation recruits more dorsal striatal circuits during specific forms of learning. A prominent hypothesis posits that reward seeking depends over time on more dorsal striatal circuits as behavioral control becomes habitual. Thus, we also ask whether activating mesolimbic dopamine systems can hasten development of habitual responding for natural or drug reward. In addition, we will determine neural signals mediating behaviors conditioned by mesolimbic dopamine activation in order to reveal neural changes in downstream neuronal populations that mediate the performance of these dopamine-mediated learned behaviors. These studies will provide new information on the separate and interactive contributions of ventral and dorsal striatal circuits to reward seeking behavior that can be initiated by dopamine, and are relevant for our understanding of behavioral disorders involving overeating and substance use disorders.

Public Health Relevance

The neurotransmitter, dopamine, plays a major role in Pavlovian and instrumental reward learning, but the specific means are unclear. Here we seek to better define that role using optogenetics, electrophysiology and pharmacology approaches in rats to test hypotheses of how dopamine neuron activity impacts learning and reward. Our goal is to clarify the independent and interactive roles of parallel dopamine-striatal circuits, thereby allowing for a deeper understanding of dopamine's contribution to normal and pathological behavior, especially as relates to substance abuse disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA035943-08
Application #
10089221
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Sorensen, Roger
Project Start
2014-04-01
Project End
2024-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
8
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Fischbach-Weiss, Sarah; Reese, Rebecca M; Janak, Patricia H (2018) Inhibiting Mesolimbic Dopamine Neurons Reduces the Initiation and Maintenance of Instrumental Responding. Neuroscience 372:306-315
Saunders, Benjamin T; Richard, Jocelyn M; Margolis, Elyssa B et al. (2018) Dopamine neurons create Pavlovian conditioned stimuli with circuit-defined motivational properties. Nat Neurosci 21:1072-1083
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Millan, E Zayra; Kim, H Amy; Janak, Patricia H (2017) Optogenetic activation of amygdala projections to nucleus accumbens can arrest conditioned and unconditioned alcohol consummatory behavior. Neuroscience 360:106-117
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