It has become increasingly clear that both spontaneous and trained behaviors engage activity throughout the cortex. However, at least in the case of perceptual decisions, task complexity critically modulates the underlying large- and mesoscale cortical dynamics. When decisions are simple sensorimotor mappings, cortical activity is correlated and behavioral effects of inactivation are essentially restricted to the relevant sensory areas. Conversely, when decisions are complex and demanding, e.g. when accumulating evidence over seconds, cortical activity becomes decorrelated and behavioral effects of inactivation are widespread, indicating distributed processes. The present proposal seeks to understand the circuit mechanisms underlying task-induced changes in large-scale cortical dynamics. In particular, I will use task switching in virtual reality, large-scale calcium imaging at mesoscale or cellular resolution, pharmacogenetics, optogenetics and recurrent neural network modeling, in isolation or combined, to test the hypothesis that the basal forebrain cholinergic system is part of the mechanism that induces large-scale decorrelations with increased task complexity. I thus aim to use a unique combination of state-of-the-art techniques to provide a detailed and causal account of how task-specific cortical states are influenced by neuromodulation. Beyond its importance for basic research, elucidating these processes will be crucial for understanding and treating the cognitive deficits caused by cholinergic dysfunction in Alzheimer’s disease and other dementias. More generally, it will also have implications for the deficits in decision-making that are a hallmark of many other brain disorders such as obsessive-compulsive disorder, attention deficit hyperactivity disorder and drug abuse
|Effective start/end date||2/1/21 → 1/31/24|
- National Institute of Mental Health (5R00MH120047-04)
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