HypoAdapt · The hypothalamic control of behavioral and physiological adaptations to stress

When faced with threats to their survival, animals execute flexible behavioral adaptations specific to each threat, such as escaping a predator. These behaviors are accompanied by brain-driven physiological changes, including elevated heart rate, blood pressure and respiration, which are critical for meeting the increased energy demands during stress. While behavioral responses to threats have been extensively studied, the neural mechanisms that coordinate the accompanying physiological changes remain poorly understood. Additionally, it remains unclear how the brain orchestrates behavioral and physiological adaptations in tandem. HypoAdapt aims to bridge this knowledge gap by investigating the organization and function of the hypothalamus — a critical brain region responsible for both behavioral and physiological responses to homeostatic challenges. Specifically, we will focus on the dorsomedial hypothalamus (DMH) through the following aims. Aim 1: Decipher the anatomical and functional organization of the DMH circuitry that controls responses to distinct stressors. Aim 2: Define how inhibitory inputs to the DMH control the dynamic execution of behavioral and physiological responses with precise timing and vigor. Aim 3: Discover the role of neuropeptide inputs to the DMH in regulating stress state by modulating the underlying neural circuits. By employing cellular resolution neural imaging, machine-learning-based behavioral tracking, monitoring of physiology and neural circuit mapping and manipulations, HypoAdapt will be the first study to offer a holistic view of the neural circuit mechanisms underlying survival adaptations to threats. These findings will illuminate general principles underlying brain-controlled processes that require both rapid and long lasting regulation. Additionally, this research has the potential to inform about mechanisms underlying dysregulation of these behavioral and physiological adaptions in stress and anxiety disorders.