This proposal seeks to explore the structure of neuronal activity in the ventral tegmental area (VTA) and its relationship with neuronal activity in the hippocampus (HC) during reinforced spatial learning. The VTA dopamine (DA) system is a key substrate of reinforcement learning that appears to underlie the internal map of value that animals use to select goals. The HC also functions in reinforced spatial learning, as it is necessary for navigation and episodic memory. In freely moving animals, in the spatial domain, VTA activity may additionally contribute to navigation towards goals. VTA GABA neurons may play a critical role in directing and regulating the encoding of value. They project to the same structures as DA cells, including the HC, and inhibit DA neurons. Locally, VTA GABA neurons may participate in the DA cell computation of reward prediction error (RPE) and may regulate DA cell output. Through their projections, GABA neurons may also dynamically select target structures for DA signaling and may provide them with DA-independent reward-related information. This study will employ multielectrode recordings of neuronal ensembles in the VTA and HC to elucidate their interactions through 3 specific aims. First, it will assess the capacity for VTA DA and GABA neurons to represent trajectories predictive of future reward. Then, it will explore the role of GABA neuronal activity in the RPE representation. Lastly, it will examine VTA-HC interactions in reinforced spatial learning in normal conditions and after pharmacological perturbations of DA function. The immediate goal of the candidate is to obtain training in multielectrode recording in the VTA and HC of awake behaving rats, sponsored by Dr. Matthew Wilson, with complementary clinical training in movement and memory disorders, sponsored by Dr. John Growdon. The many resources of the lab and MIT neuroscience community will thus be enhanced by those of Harvard University and Massachusetts General Hospital. The long- term goal is to learn how the VTA contributes to normal and aberrant cognitive control, through its intrinsic circuitry and interactions with other brain regions. Given the pivotal role of the DA system in reinforcement learning, cognitive control, Parkinson's disease, drug addiction, and schizophrenia, and the importance of the HC in episodic memory, spatial navigation, and schizophrenia, insights into VTA function and the mechanisms by which it communicates with brain areas such as the HC will have high clinical relevance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08MH081027-02
Application #
7626377
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Desmond, Nancy L
Project Start
2008-06-01
Project End
2013-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
2
Fiscal Year
2009
Total Cost
$174,005
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Chen, Zhe; Gomperts, Stephen N; Yamamoto, Jun et al. (2014) Neural representation of spatial topology in the rodent hippocampus. Neural Comput 26:1-39