Prefrontal-subcortical circuitry underlying cognitive flexibility

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The ability to use information flexibly and execute appropriate behaviours in response to changing environmental conditions is essential for survival in all species. In some instances, flexible behaviours enable more efficient pursuits of rewards (such as food), whereas in other situations, these processes aid in reorganizing behavior to deal with potential aversive consequences. Work by our group has shown that different components of cognitive flexibility are dependent on functional interactions between the frontal lobes and a variety of subcortical systems. However, important questions remain regarding the cellular and neurochemical mechanisms that underlie the interplay between these circuits in the mediation of these types of executive functioning. For example, it is currently unknown how neural activity within these different regions that is associated with specific events of the learning process (eg; before action selection or after action outcomes) serves to facilitate changes in behavior. In addition, our understanding of the brain circuitry and neurochemistry underlying flexible responding in aversively-motivated situations is limited. With these issues in mind, the present research proposal has two main objectives;*** 1) Explore the neural basis underlying strategy shifting and probabilistic reversal learning in different regions of the frontal lobes and ventral striatum and the interactions between these systems, using temporally-precise optogenetic silencing.*** 2) Map out the neural circuitry linked with the dopamine system that facilitates different forms of aversively-motivated behaviors, using traditional approaches that have proven fruitful in exploring other forms of flexibility. These behaviors include those requiring discrimination between stimuli linked to aversive vs neutral outcomes and aversive conditioning, and those requiring an organism to flexibly regulate making or withholding responses to avoid punishments. *** By utilizing a circuitry analysis approach combined with optogenetic and traditional behavioural pharmacological methods, this research will provide valuable insight into the mechanisms by which different nodes within the prefrontal-striatal circuitry interact to regulate strategy selection and cognitive flexibility for both appetitive and aversively-motivated behaviors. As such, this line of research ultimately will lead to a greater understanding of how distributed neural networks regulate adaptations of behaviour that promote survival.