Neurobiology of Metabolism, Nutrition & Stress Response Laboratory

The Neurobiology of Metabolism, Nutrition and Stress Response Laboratory at the Psychiatry Research Institute at Montefiore Einstein (PRIME) focuses on the connection between stress response and energy metabolism across different developmental stages, examining how stress and snacking can lead to outcomes such as obesity or anorexia.

Our research aims to further understand how the brain coordinates the response to the body’s metabolic needs and motivational drives, how the environment influences these responses and how underlying biology can lead to a broad spectrum of adaptive and disease-related outcomes.

Our research employs a clinically informed systems neuroscience approach; diverse experimental strategies, such as optogenetics and calcium imaging; molecular approaches, such as mouse genetics and viral tracing; and classical surgical manipulations and pharmacologic electrophysiology. We focus our investigations primarily on circuits involving G-protein-coupled receptors genetically linked to human disease.

Through these combined approaches, we aim to identify the molecules, cell types, circuit connections and activity patterns that drive feeding-related behavior and energy metabolism in response to stress and how these interconnections become dysregulated in disease states.

Our translational laboratory uses systems neuroscience tools to better understand the pathophysiology and biology that underlie the behavior related to these diseases, in hopes of reducing the associated stigma. We are focused on how neuropeptides regulate specific circuits at the interface of stress and metabolism.

Current research concentrates on two neuropeptidergic systems: the metabolism-associated melanocortinergic system and the stress-linked pituitary adenylate cyclase-activating polypeptide (PACAP) system. In rodent models, we use a combination of behavioral studies, electrophysiology, in vivo calcium (Ca2+) imaging, and pharmacologic, optogenetic and chemogenetic manipulations to interrogate how these neuropeptides regulate neural circuits at the interface of stress and metabolism.

Collaborating with clinical researchers, we apply our findings to inform investigations into human behavior using molecular, genetic and qualitative approaches.

Our current research focus includes the following queries:

• What is the role of the melanocortin-4 receptor in the medial prefrontal cortex in cognitive flexibility? Is it specific to food-related decision-making? How do neurocircuit responses of males and females in different states lead to different body weight and food intake-related outcomes?
• Does metabolic stress transmit a PACAPergic signal, and how is this different between males and females? How does this affect the reproductive axis?
• How does dietary manipulation affect behavioral outcomes?
• How does early life food insecurity disrupt the coordination of stress and metabolic neuroendocrine signaling, which is critical to healthy development, physiology and behavior?
• What is the role of melanocortin signaling in human syndromes of obesity and cognitive dysfunction (e.g. Prader-Willi syndrome and Bardet-Biedl syndrome)?