2. Academic Validation
  3. Molecularly defined and functionally distinct cholinergic subnetworks

Molecularly defined and functionally distinct cholinergic subnetworks

  • Neuron. 2022 Sep 14;S0896-6273(22)00796-6. doi: 10.1016/j.neuron.2022.08.025.
Xinyan Li 1,  Hongyan Yu 2,  Bing Zhang 2,  Lanfang Li 2,  Wenting Chen 1,  Quntao Yu 2,  Xian Huang 2,  Xiao Ke 2,  Yunyun Wang 3,  Wei Jing 2,  Huiyun Du 1,  Hao Li 2,  Tongmei Zhang 4,  Liang Liu 3,  Ling-Qiang Zhu 5,  Youming Lu 6
Affiliations

Affiliations

  • 1 Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 4030030, China; Institute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 2 Institute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 3 Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 4 Institute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 5 Institute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: [email protected].
  • 6 Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 4030030, China; Institute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: [email protected].
PMID: 36130594 DOI: 10.1016/j.neuron.2022.08.025
Abstract

Cholinergic neurons in the medial septum (MS) constitute a major source of cholinergic input to the forebrain and modulate diverse functions, including sensory processing, memory, and attention. Most studies to date have treated cholinergic neurons as a single population; as such, the organizational principles underling their functional diversity remain unknown. Here, we identified two subsets (D28K+ versus D28K-) of cholinergic neurons that are topographically segregated in mice, Macaca fascicularis, and humans. These cholinergic subpopulations possess unique electrophysiological signatures, express mutually exclusive marker genes (kcnh1 and aifm3 versus cacna1h and gga3), and make differential connections with physiologically distinct neuronal classes in the hippocampus to form two structurally defined and functionally distinct circuits. Gain- and loss-of-function studies on these circuits revealed their differential roles in modulation of anxiety-like behavior and spatial memory. These results provide a molecular and circuitry-based theory for how cholinergic neurons contribute to their diverse behavioral functions.

Keywords

anxiety-like behaviors; calbindin D28K; cholinergic neurons; hippocampus; medial septum; spatial memory.

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