Behavioral flexibility is the ability to adapt to a changing and uncertain environment (Kolb, 1990). The prefrontal cortex (PFC) is the neural substrate of behavioral flexibility (Fuster, 2001), and its subcircuits may provide different facets of adaptive learning. For example, the orbitofrontal cortex (OFC), part of the ventral aspect of the PFC, is critical in guiding behavior when stimulus-outcome associations change (Wallis, 2007; Schoenbaum et al., 2009b; Rhodes & Murray, 2013; Stalnaker et al., 2015), especially when they are noisy (Noonan et al., 2010; Dalton et al., 2016). Another subregion of the PFC, the medial PFC (mPFC), is crucial for adaptive responses in a quickly changing, or volatile environment (Behrens, 2007; Guise & Shapiro, 2017). The exact contribution and cooperation between these regions remains unknown. Cognitive flexibility and orchestrated PFC activity is distorted in people with neuropsychiatric disorders (Reeck et al., 2015). Elucidating these mechanisms will be key to finding cures to serious conditions. The goal of this project was to investigate the roles of prefrontal subregions OFC and mPFC to adaptive behavior in a reversal-learning paradigm.
Behavioral experiments demonstrated that: 1) mPFC is needed for reversing a deterministic and probabilistic spatial contingency, but not for acquiring a spatial rule, 2) the OFC is not needed for reversing a deterministic or probabilistic spatial contingency, or acquiring a spatial rule, and 3) mPFC-OFC interactions are required for reversing a deterministic and probabilistic spatial contingency, but not acquiring a spatial rule. We carried out further behavioral experiments and showed that: 1) reversal-learning deficits are contingent upon the amount of training or experience an animal has had with reversal learning, and 2) mPFC and OFC inactivation did not slow the rate of reversal learning acquisition in animals with no previous experience with reversal learning. Finally, quantitative models of behavior showed that: 1) naïve animals, and trained animals without an mPFC process reward history similarly, 2) reinforcement learning shows that the learning rate increases across training. Together these results suggest the mPFC is critical for learning to learn.
|Commitee:||Baxter, Mark, Laubach, Mark, Rich, Erin, Rudebeck, Peter, Schiller, Daniela|
|School:||Icahn School of Medicine at Mount Sinai|
|School Location:||United States -- New York|
|Source:||DAI-B 80/11(E), Dissertation Abstracts International|
|Subjects:||Neurosciences, Cognitive psychology|
|Keywords:||MPFC, OFC, Prefrontal cortex, Reversal learning|
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