MULTISENSORY INTEGRATION BY BRAINSTEM PEPTIDERGIC NEURONS REGULATING FEEDING BEHAVIOR

The brainstem functions as the central hub controlling moment-to-moment ingestive behavior. The ending of an ongoing meal is a major factor in determining meal size and, therefore, influences energy intake and body weight. Meal termination in an adaptive setting is called satiation, which is dissociable from satiety signaling (the state between two consecutive meals) and is regulated by a distinct set of neural circuits. While hypothalamic peptidergic neurons are crucial for regulating hunger-satiety dynamics, classic studies using decerebrate rats identified a satiation center in the brainstem. However, the specific cell types, circuits, and mechanisms that govern brainstem regulation of satiation remain poorly understood. In recent work, we describe the discovery of an obligate peptidergic population in the brainstem’s dorsal raphe nucleus that controls satiation. These neurons express the anorectic hormone cholecystokinin (CCK) and an array of other peptides, while lacking classical fast neurotransmitters. Input-output mapping revealed that CCK neurons are ideally positioned to coordinate with other feeding-related brain areas. The regulatory effect of CCK neurons on feeding exhibits a built-in delay and persists for tens of minutes even after their activity ceases. To achieve this, CCK neurons integrate various ingestive signals. These signals include the sensory qualities of food, oropharyngeal signals from the bite, the chemical sensation of food macronutrients in the stomach, and gut-derived humoral factors. This multilevel sensory integration, with its delayed yet sustained effect on food intake, makes the CCK population a prime candidate for the elusive "satiation center" in the brainstem.