Neuronal subtypes study uncovers parallel gut-to-brain pathways that regulate feeding behaviors

The ability to regulate one’s own food intake is essential to the survival of both humans and other animals. This innate ability ensures that the body receives the nutrients it needs to perform daily activities, without significantly exceeding calorie intake, which could lead to health problems and metabolic disorders.

Past neuroscience studies suggest that the regulation of food intake is supported by specific regions in the brain, including the hypothalamus and caudal nucleus of the solitary tract (cNTS), which is part of the brainstem. This key region in the brainstem is known to integrate sensory signals originating from the gut and then transform them into adaptive feeding behaviors.

While previous research has highlighted the key role of the cNTS in food intake regulation, the unique contribution of the different neuron subtypes within this brainstem region and the mechanisms by which they regulate feeding remain poorly understood. Better understanding these neuron-specific mechanisms could help to devise more effective therapeutic interventions for obesity and eating disorders.

Researchers at the Chinese Institute for Brain Research and other institutes in China recently carried out a study aimed at identifying neuronal subtypes in the mouse cNTS that are involved in how mice control their feeding behaviors. Their findings, published in Nature Neuroscience, show that different types of cNTS neurons process gut-originating signals via distinct sensory pathways, collectively contributing to the regulation of feeding.

“The cNTS in the brainstem serves as a hub for integrating interoceptive cues from diverse sensory pathways,” wrote Hongyun Wang, Runxiang Lou and their colleagues in their paper. “However, the mechanisms by which cNTS neurons transform these signals into behaviors remain debated. We analyzed 18 cNTS-Cre mouse lines and cataloged the dynamics of nine cNTS cell types during feeding.”

The researchers systematically analyzed the brains and feeding behaviors of mice that were genetically intervened upon to turn “off” and “on” nine types of neurons in the cNTS. The researchers found that two key neuron populations, namely Th⁺ (tyrosine hydroxylase-expressing) and Gcg⁺ (glucagon-like peptide 1-expressing) neurons encoded different aspects of food intake.

“We show that Th⁺ cNTS neurons encode esophageal mechanical distension and transient gulp size via vagal afferent inputs, providing quick feedback regulation of ingestion speed,” wrote Wang, Lou and their colleagues.

“By contrast, Gcg⁺ cNTS neurons monitor intestinal nutrients and cumulative ingested calories and have long-term effects on food satiation and preference. These nutritive signals are conveyed through a portal vein–spinal ascending pathway rather than vagal sensory neurons.”

This recent study by Wang, Lou and their colleagues gathered new important insight about the mechanisms via which neurons in the cNTS regulate feeding behaviors in mice. New studies could explore the unique contribution of the two broad neuron populations outlined by the researchers (i.e., Th⁺ and Gcg⁺ neurons), as well as their interactions with other brain regions in regulating feeding behaviors.

“Our findings underscore distinctions among cNTS subtypes marked by differences in temporal dynamics, sensory modalities, associated visceral organs and ascending sensory pathways, all of which contribute to specific functions in coordinated feeding regulation,” wrote the researchers.

In the future, the studies carried out by this research group could help to identify new promising therapeutic targets for treating obesity and eating disorders. Meanwhile, Wang, Lou and their colleagues will continue exploring the role of the different cNTS neuron subtypes they identified in food intake control.

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