Luo Lingli, Jing Wei, Guo Yiqing, Liu Dan, He Aodi, Lu Youming
Innovation Center of Brain Medical Sciences, Ministry of Education of the People's Republic of China, Huazhong University of Science and Technology, Wuhan, China.
Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Nat Commun. 2025 Apr 10;16(1):3417. doi: 10.1038/s41467-025-58591-y.
Major depression is characterized by an array of negative experiences, including hopelessness and anhedonia. We hypothesize that inhibition of negative experiences or aversion may generate antidepressant action. To directly test this hypothesis, we perform multimodal behavioral screenings in male mice and identify somatostatin (SST)-expressing neurons in the region X (HBX) between the lateral and medial habenula as a specific type of antidepressant neuron. SST neuronal activity modulation dynamically regulates antidepressant induction and relief. We also explore the circuit basis for encoding these modulations using single-unit recordings. We find that SST neurons receive inhibitory synaptic inputs directly from cholecystokinin-expressing neurons in the bed nucleus of the stria terminalis and project excitatory axon terminals onto proenkephalin-expressing neurons in the interpeduncular nucleus. This study reveals a cell-type-specific circuit of SST neurons in the HBX that encodes antidepressant action, and the control of the circuit may contribute to improving well-being.
重度抑郁症的特征是一系列负面体验，包括绝望和快感缺失。我们假设抑制负面体验或厌恶感可能产生抗抑郁作用。为了直接验证这一假设，我们在雄性小鼠中进行了多模式行为筛查，并确定了外侧缰核和内侧缰核之间的X区域（HBX）中表达生长抑素（SST）的神经元是一种特定类型的抗抑郁神经元。SST神经元活动调节动态调控抗抑郁诱导和缓解。我们还使用单细胞记录探索了编码这些调节的神经回路基础。我们发现，SST神经元直接从终纹床核中表达胆囊收缩素的神经元接收抑制性突触输入，并将兴奋性轴突终末投射到脚间核中表达前脑啡肽的神经元上。这项研究揭示了HBX中SST神经元的一种细胞类型特异性神经回路，该回路编码抗抑郁作用，对该神经回路的控制可能有助于改善幸福感。
