Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Division of Gastroenterology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
Cell. 2023 Aug 3;186(16):3368-3385.e18. doi: 10.1016/j.cell.2023.07.007.
The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology and gastrointestinal (GI) disease. Here, we report genetically defined subsets of colon-innervating DRG neurons with diverse morphologic and physiologic properties. Four colon-innervating DRG neuron populations are mechanosensitive and exhibit distinct force thresholds to colon distension. The highest threshold population, selectively labeled using Bmpr1b genetic tools, is necessary and sufficient for behavioral responses to high colon distension, which is partly mediated by the mechanosensory ion channel Piezo2. This Aδ-HTMR population mediates behavioral over-reactivity to colon distension caused by inflammation in a model of inflammatory bowel disease. Thus, like cutaneous DRG mechanoreceptor populations, colon-innervating mechanoreceptors exhibit distinct anatomical and physiological properties and tile force threshold space, and genetically defined colon-innervating HTMRs mediate pathophysiological responses to colon distension, revealing a target population for therapeutic intervention.
支配远端结肠的背根神经节（DRG）神经元的特性尚未明确，这阻碍了我们对其在正常生理和胃肠道（GI）疾病中的作用的理解。在这里，我们报告了具有不同形态和生理特性的经基因定义的结肠传入 DRG 神经元亚群。四个结肠传入 DRG 神经元群对机械刺激敏感，并表现出不同的力阈值来响应结肠扩张。使用 Bmpr1b 遗传工具选择性标记的最高阈值群体，对于对高结肠扩张的行为反应是必要和充分的，其部分由机械感觉离子通道 Piezo2 介导。在炎症性肠病模型中，这种 Aδ-HTMR 群体介导了对炎症引起的结肠扩张的过度反应。因此，与皮肤 DRG 机械感受器群体一样，结肠传入机械感受器表现出不同的解剖和生理特性以及力阈值空间，并且经基因定义的结肠传入 HTMR 介导对结肠扩张的病理生理反应，揭示了治疗干预的目标群体。
