Hypothalamic pro-opiomelanocortin (POMC) neurons are canonically recognized as key anorexigenic neurons in the melanocortin circuit with a role in satiety and energy homeostasis. However, optogenetic stimulation does not decrease feeding behavior during ad-lib fed animals in a physiologically relevant manner. This suggests that there are possible nuances in their activity dynamics such as timing (when a neuron is active in relation to a specific behavior), direction (inhibition or excitation), or specificity (if only certain subgroups of POMC neurons are active). POMC neurons in the hypothalamus are a molecularly diverse population, which suggests that they would display diverse neuronal activity responses during various ingestive behaviors.
Currently, single-cell recordings of hypothalamic POMC neurons has never been investigated in behaving animals. Using one-photon microendoscopic calcium imaging, we characterized the neuronal activity dynamics of individual hypothalamic neurons during a broad range of feeding behaviors prior to, during, and after ingestion, during different metabolic states in mice.
We show that hypothalamic POMC neurons are highly engaged during food-seeking, consumption of different nutrients, and post-ingestive responses related to circulating molecules relaying metabolic information. Individual hypothalamic POMC neurons show diverging responses in terms of valence, duration, magnitude, and timing to different feeding behaviors that are responsive to intercurrent metabolic status.
Our results suggest that hypothalamic POMC neurons may integrate moment-to-moment metabolic status with feeding and food-seeking actions at short- and long-term scales to implement behaviors and autonomic responses to coordinate complex components of energy homeostasis.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/h4sb-f584 |
| Date | January 2024 |
| Creators | Li, Xueting |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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