Our decisions are powerfully shaped by internal states (such as hunger or thirst) and external representations driven by sensory inputs. A fundamental question is how these sources of information interact to produce flexible decision-making strategies that are adaptive and achieve desired outcomes. Flexible decision-making underlies complex cognitive functions like problem-solving and reasoning, and goes awry in neuropsychiatric disorders like schizophrenia, anxiety, and addiction. The vastly interconnected cortical and subcortical systems of the brain are crucial neural substrates for the adaptive control of behavior. Yet, the organizing principles for how interactions within and between these systems support flexible decision-making behaviors have remained elusive.

Prefrontal cortex (PFC) and thalamic areas have access to both internal and external representations via converging inputs from multiple brain areas. These areas in turn provide diverging outputs, allowing them to rapidly reconfigure brain-wide processes to guide decision-making. Our overarching hypothesis is that specific PFC and thalamic neuronal populations facilitate flexible decision-making by recruiting specialized ensembles of neurons in their target structures. A significant challenge in testing this hypothesis has been the lack of tools for selectively probing the activity of defined neuronal populations. However, recent advancements in optical techniques for recording and manipulating neuronal activity with high spatiotemporal resolution, combined with methods for targeting neuronal populations based on their genetic and/or anatomical identity, finally make this a tractable problem to solve.

The long-term research goal of our lab is to understand how cell specific cortical and subcortical circuits support flexible control of behavior. We address this question by integrating a portfolio of cutting-edge techniques including 1) large scale cellular and subcellular resolution two-photon calcium imaging to measure the activity patterns of specific neuronal populations; 2) sophisticated and quantifiable behavioral paradigms for mice that probe core features of adaptive behavioral control; 3) targeted optogenetic manipulations to determine the causal relationship between neuronal activity and behavior; and 4) advanced circuit tracing tools to establish the structural logic of connectivity between specific neuronal populations. Collectively, this research program will deconstruct the neural circuits that enable flexible decision-making and reveal the organizing principles for how the vastly interconnected networks of the brain process internal and external information to produce goal-oriented behaviors.