What allows us to link particular visual stimuli with particular actions? We frequently and rapidly form different types of associations. Some associations can be as simple as learning that red means stop, while green means go. More complex associations can include a baseball player learning to swing at a pitch thrown in the strike zone. In general, humans and primates share a remarkable ability to rapidly adjust or modify associations between visual cues and specific motor responses in order to maximize reward. However, surprisingly little is known regarding how such associations are formed in the brain. Recent learning models suggest that the neostriatum, which is part of a larger group of nuclei called the basal ganglia, is optimally positioned to play a role in this process. Historically, studies of the basal ganglia have focused on their role in motor control. However, recent data suggests that the basal ganglia play a crucial role in associative learning. This new emphasis on learning takes into account data from both anatomic and physiologic studies and has the potential to unify what were previously disparate or paradoxical aspects of basal ganglia function. Therefore, the goal of the experiments described here is to systematically examine the role of the basal ganglia in learning new visual-motor associations using awake-behaving primates as our model. We will use a multidisciplinary approach involving novel behavioral learning tasks, direct microstimulation, and direct assessments of dopamine release, in order to elucidate the role of the neostriatum in associative learning. Our general hypothesis is that the dorsal neostriatum is a site where specific visual-motor associations are formed and enhanced. We believe that this process occurs by the reinforcement of particular circuits and that this reinforcement is mediated by the neurotransmitter dopamine. The results of this research will have profound implications for our comprehension of the brain mechanisms underlying learning and for our understanding of the role of the basal ganglia in general. Disruption of basal ganglia processing has been implicated in a number of disabling neurological diseases such as Parkinson Disease, Tourette syndrome and Autism. This proposal will shed considerable light on the role of basal ganglia in movement disorders and learning disorders. In addition, it will potentially provide the basis for their rational treatment using techniques such as deep brain stimulation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY017658-05
Application #
8133829
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Steinmetz, Michael A
Project Start
2007-08-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$419,958
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Patel, Shaun R; Herrington, Todd M; Sheth, Sameer A et al. (2018) Intermittent subthalamic nucleus deep brain stimulation induces risk-aversive behavior in human subjects. Elife 7:
Martinez-Rubio, Clarissa; Paulk, Angelique C; McDonald, Eric J et al. (2018) Multimodal Encoding of Novelty, Reward, and Learning in the Primate Nucleus Basalis of Meynert. J Neurosci 38:1942-1958
Asaad, Wael F; Lauro, Peter M; Perge, János A et al. (2017) Prefrontal Neurons Encode a Solution to the Credit-Assignment Problem. J Neurosci 37:6995-7007
Lee, Karen E; Bhati, Mahendra T; Halpern, Casey H (2016) A Commentary on Attitudes Towards Deep Brain Stimulation for Addiction. J Neurol Neuromedicine 1:1-3
Katnani, Husam A; Patel, Shaun R; Kwon, Churl-Su et al. (2016) Temporally Coordinated Deep Brain Stimulation in the Dorsal and Ventral Striatum Synergistically Enhances Associative Learning. Sci Rep 6:18806
Mian, Matthew K; Sheth, Sameer A; Patel, Shaun R et al. (2014) Encoding of rules by neurons in the human dorsolateral prefrontal cortex. Cereb Cortex 24:807-16
Patel, Shaun R; Ghose, Kaushik; Eskandar, Emad N (2014) An open source 3-d printed modular micro-drive system for acute neurophysiology. PLoS One 9:e94262
Gale, John T; Lee, Kendall H; Amirnovin, Ramin et al. (2013) Electrical stimulation-evoked dopamine release in the primate striatum. Stereotact Funct Neurosurg 91:355-63
Patel, Shaun R; Sheth, Sameer A; Martinez-Rubio, Clarissa et al. (2013) Studying task-related activity of individual neurons in the human brain. Nat Protoc 8:949-57
Srinivasan, Lakshminarayan; Asaad, Wael F; Ginat, Daniel T et al. (2013) Action initiation in the human dorsal anterior cingulate cortex. PLoS One 8:e55247

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