Brain-wide input-output analysis of tuberal nucleus somatostatin neurons reveals hierarchical circuits for orchestrating feeding behavior.

Feeding is an innate behavior critical for survival but is also influenced by many non-nutritional factors such as emotion, social context and environmental conditions. Recently, tuberal nucleus somatostatin (SST) neurons have been identified as a key feeding regulation node. To gain a deeper understanding of the SST neural networks, we quantitatively characterised the brain-wide input-output configuration of mice SST neurons using the VITALISTIC method (Viral Tracing Assisted by Light-Sheet microscope and Tissue Clearing) and single-cell projectomes by fluorescence micro-optical sectioning tomography (fMOST). We found that SST neurons receive direct inputs from and send outputs to a broad range of brain regions, including many cortical and subcortical areas. Differently from AgRP neurons, the extensively studied 'hunger' neurons, SST neurons receive more diverse inputs from extra-hypothalamic regions and neuromodulatory centers. Using the projection-specific input tracing, we further revealed fine-tuning of the input-output configuration of SST neurons that align with specific functional needs.