Neural mechanisms underlying behavioral flexibility

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Adaptive behaviours in stochastic environments are critical for future success and survival. In the natural environment, animals need to typically make decisions in a timely manner, assess outcomes to avoid undesirable ones, and update their choice patterns and behaviour accordingly, to promote flexible responding.A long line of studies showing that lesioning of striatal cholinergic interneurons (which release acetylcholine), and pharmacological manipulation of ACh release impaired behavioural flexibility. Notwithstanding, the precise role of ACh in mediating behavioural switching processes, when conditions demand a shift in response, is lacking. Of important relevance are the processes that regulate and mediate the disengagement of old, invalid information, and the engagement of new, valid information on reinforcement contingencies in the striatum. So far, we have successfully designed a behavioural task using a virtual reality system integrated with 2-photon microscope. Using this, we have also commenced simultaneous imaging of ACh release in striatum while mice are engaged in a task with rule switches. Preliminary results show that dynamic spatiotemporal patterning by ACh is a possible way for contextual responses of cholinergic interneurons to integrate context and reward to facilitate behavioral flexibility.