Zhang Yufen, Liu Fang, Yang Lite, Hahm Hannah J, Heitmeier Monique R, Okuda Takao, Kawatani Masahiro, Harrigan Jahnia T, Morrison-Rodriguez Erica C, Petukhova Anna, Lu Zhaotong, Heitmeier Harry A, Samineni Vijay K
Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, United States.
Neuroscience Graduate Program, Division of Biology & Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States.
bioRxiv. 2025 Sep 1:2025.08.27.672386. doi: 10.1101/2025.08.27.672386.
End-organs such as the bladder rely on a delicate balance between internal urgency and voluntary restraint. However, the specific spinal circuits coordinating these functions remain poorly defined. Here, we identify a genetically defined population of lumbosacral spinal interneurons marked by expression that gate bladder sensory input and regulate micturition reflexes. Single-cell transcriptomics and in situ physiology reveal molecularly distinct subtypes. Functional manipulation reveals that neurons are essential for coordinating bladder-sphincter activity and gating visceral pain. Their ablation leads to bladder hypersensitivity and voiding dysfunction, while targeted activation reverses these maladaptive states. Circuit tracing reveals convergence of primary afferent and descending brainstem inputs onto neurons. These findings establish interneurons are critical for bladder sensory-motor integration and extend classical spinal gating models to encompass visceral pain and organ reflex control.
诸如膀胱等终末器官依赖于内部紧迫感与自主抑制之间的微妙平衡。然而,协调这些功能的特定脊髓回路仍未明确界定。在这里,我们鉴定出一群由 表达标记的腰骶部脊髓中间神经元,它们控制膀胱感觉输入并调节排尿反射。单细胞转录组学和原位生理学揭示了分子上不同的 亚型。功能操作表明, 神经元对于协调膀胱 - 括约肌活动和控制内脏疼痛至关重要。它们的消融导致膀胱超敏反应和排尿功能障碍,而靶向激活则逆转这些适应不良状态。回路追踪揭示了初级传入和下行脑干输入汇聚到 神经元上。这些发现表明 中间神经元对于膀胱感觉 - 运动整合至关重要,并将经典的脊髓门控模型扩展到包括内脏疼痛和器官反射控制。