Cortico-thalamic-striatal circuitry and cognitive flexibility

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The ability to use information flexibly and execute appropriate adaptive behaviours in response to changing environmental conditions is essential for survival in all species. The prefrontal cortex (PFC) is one region that is critical in facilitating cognitive flexibility by inhibiting the execution of a previous strategy to permit the emergence of new behaviours. However, important questions remain regarding the cellular and neurochemical mechanisms that underlie the interplay between these circuits in the mediation of this type of executive functioning. This research is designed to further clarify how the brain solves these types of problems in rodents, using a multidisciplinary approach. We will investigate how dopamine, a brain chemical important for movement, reward and cognition, acts in a region termed the ventral striatum, to facilitate changes in behaviour. Other experiments will use novel molecular techniques to identify what role changes in the strengths of synapses play in adjusting behaviour to changes in one's environment. In another aim, we will record neural activity from awake, behaving animals performing tasks that require them to behave in a flexible manner. This will enable us to identify the specific codes that neurons in regions such as the PFC use to signal that the environment has changed and that the animal's behaviour must change with it. The present research proposal will provide valuable insight into the mechanisms by which the PFC and related subcortical nuclei interact to regulate strategy selection and cognitive flexibility. These studies will ultimately will lead to a greater understanding of how distributed neural networks in the mammalian brain regulate an animal's ability to deal with changes in its environment and adapt its behaviour accordingly to promote its survival. Furthermore, in light of the fact that a number of mental disorders are associated with impairments in cognitive flexibility, the results of these studies may offer important insight into the neural dysfunction that underlies these conditions.