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

Journal: Nature communications
Published Date:

Abstract

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.

Authors

  • Esra Senol
    Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
  • Menghan Wang
    Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Department of Epidemiology and Biostatistics, School of Public Health, Global Health Institute Xi'an Jiaotong University Health Science Center Xi'an Shaanxi China.
  • Yongjuan Xin
    Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
  • Zhuolei Jiao
    Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
  • Hasan Mohammad
    Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
  • Xin Yi Yeo
    Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
  • Tengxiao Si
    State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, China.
  • David M Young
    Institute of Molecular and Cell Biology, A*STAR, Singapore 138673, Singapore.
  • Hua Huang
    Department of Radiology, National Cancer Center/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
  • Yingxue Wang
    Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
  • Qin Li
    Department of Spine Surgery, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China.
  • Sang Yong Jung
    Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
  • Xiaohong Xu
    The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510260, China.
  • Pei Zhang
    School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
  • Yu Fu
    Molecular Diagnosis and Treatment Center for Infectious Diseases Dermatology Hospital Southern Medical University Guangzhou China.