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Stress-induced modulation of neural circuits that regulate defensive behaviors

Inhibition of lateral septal (LS) neurons that express the type 2 corticotropin-releasing factor receptor (Crfr2) suppresses, while stimulation enhances, persistent stress-induced anxious behaviors. Despite their critical functional role however, it is unknown how or why this neuronal population stress-dependently influences behavioral state; for example:

1) How do stressful stimuli alter natural neural activity patterns in LS Crfr2-expressing neurons to tune the severity of stress-induced behavioral states? What are the consequences of such altered activity?

2) How do specific inputs and neuromodulators stress-dependently regulate LS Crfr2 neuronal function?

3) How might perturbations of key neural or molecular regulators of LS Crfr2 neurons result in abnormal behavioral states such as hypervigilance or depressive-like states?

Using a combination of molecular genetics, viral tracing, electrophysiology, and ex vivo & in vivo imaging, we are determining how neural activity in LS Crfr2+ circuitry is modulated by stress, the behavioral and physiological consequences of specific activity patterns, and the underlying cellular and molecular mechanisms.