Abstract:
Adaptive defensive responses—ranging from freezing to flight—are orchestrated by distributed neural circuits linking the amygdala, prefrontal cortex, and brainstem. Dysregulation of these systems contributes to stress-related disorders such as PTSD, yet the mechanisms governing defensive state selection and learning remain incompletely understood. In this seminar, I will highlight recent work from my lab on the circuit and neuromodulatory control of defensive behavior. Using a novel conditioned flight paradigm, we identify how central amygdala microcircuits and projections from the dorsal peduncular cortex regulate behavioral transitions and arousal. In parallel, we investigate how acetylcholine release within the basolateral amygdala and medial prefrontal cortex shapes cue salience, plasticity, and memory strength during aversive learning. Through optogenetics, fiber photometry, and neurotransmitter sensors, we uncover how basal forebrain cholinergic inputs bias defensive output and contribute to individual differences in trauma susceptibility. Together, these findings outline a circuit framework in which local inhibitory networks and cholinergic modulation jointly govern the acquisition and expression of defensive behaviors, offering new insight into pathways that may be targeted to prevent or treat maladaptive fear.