A neural circuit for excessive feeding driven by environmental context in mice

Area of Science:

• Neuroscience
• Metabolism
• Behavioral Science

Background:

• Obesity stems from overconsumption, influenced by physiological, cognitive, and environmental factors.
• Eating in obese individuals is often driven by external cues rather than internal hunger signals.
• The mechanisms by which environmental context influences non-homeostatic feeding remain unclear.

Purpose of the Study:

• To identify neural circuits mediating environmental control of feeding behavior.
• To investigate the role of hypothalamic somatostatin (SST) neurons in non-homeostatic feeding.
• To elucidate how palatable food and environmental context interact to drive overeating.

Main Methods:

• Identification and characterization of somatostatin (SST) neurons in the mouse hypothalamic tuberal nucleus.
• Optogenetic activation and inhibition of specific neuronal populations in vivo.
• Electrophysiological recordings to assess synaptic plasticity.
• Behavioral paradigms to measure food consumption in response to environmental cues.

Main Results:

• A specific population of hypothalamic tuberal nucleus somatostatin (TN-SST) neurons was found to be activated by palatable food.
• Activation of TN-SST neurons induced non-homeostatic feeding in satiated mice, dependent on subicular inputs.
• Environmental context paired with palatable food potentiated synaptic transmission onto TN-SST neurons.
• Inhibition of TN-SST neurons or the subiculum selectively suppressed this context-driven feeding.

Conclusions:

• Hypothalamic TN-SST neurons form a critical circuit linking environmental context and palatable food.
• This circuit drives non-homeostatic feeding, contributing to overconsumption.
• Understanding this pathway offers potential targets for obesity interventions.