Genetically and functionally defined NTS to PBN brain circuits mediating anorexia.

Area of Science:

• Neuroscience
• Metabolic Homeostasis
• Appetite Regulation

Background:

• The central nervous system regulates food intake to maintain metabolic balance.
• Gut signals activate neurons in the nucleus of the solitary tract (NTS) via the vagus nerve, influencing feeding behavior.
• A previously identified appetite suppression circuit involves calcitonin gene-related protein (CGRP)-expressing neurons in the lateral parabrachial nucleus (PBN).

Purpose of the Study:

• To identify the molecular identity of neurons that directly excite CGRP-expressing PBN neurons.
• To elucidate the neural pathways involved in appetite suppression.

Main Methods:

• Optogenetic and chemogenetic activation of specific neuronal populations in the NTS.
• Identification of neuronal inputs to CGRP(PBN) neurons using molecular markers.
• Assessment of food intake and body weight changes in response to neuronal stimulation.

Main Results:

• Cholecystokinin (CCK) and dopamine β-hydroxylase (DBH)-expressing NTS neurons were identified as direct excitatory inputs to CGRP(PBN) neurons.
• Activation of these CCK and DBH NTS neurons significantly decreased food intake.
• Chronic stimulation of these NTS neurons resulted in body weight loss in mice.

Conclusions:

• CCK and DBH neurons in the NTS directly activate CGRP(PBN) neurons to promote anorexia.
• This study reveals a novel neural circuit for appetite suppression originating from the gut.
• Targeting these identified neurons may offer therapeutic strategies for obesity and metabolic disorders.