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The ability to withhold a response is a core component of executive function, and it is compromised across a wide range of neuropsychiatric conditions. The prefrontal cortex relies on converging neuromodulatory input to support this function, and chronic stress readily degrades it. We use optical recording of neuromodulator dynamics, cell-type-and projection-specific manipulation, and rodent behavioral paradigms that require action suppression to ask how neuromodulatory signals in the prefrontal cortex index inhibitory control, and how chronic stress reorganizes those signals.

The locus coeruleus is among the earliest sites of pathology in Alzheimer's disease, showing degeneration years before cognitive symptoms emerge. Using mouse models of amyloid and tau pathology together with chemogenetic control of the LC and behavioral testing, we examine how noradrenergic activity interacts with pathology over time, with the longer-term goal of evaluating neuromodulation as a therapeutic strategy.