Optical recording reveals topological distribution of functionally classified colorectal afferent neurons in intact lumbosacral DRG
Optical recording reveals topological distribution of functionally classified colorectal afferent neurons in intact lumbosacral DRG
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DOI：
10.14814/phy2.14097
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发表时间：
2019-05-01
影响因子：
2.5
通讯作者：
Feng, Bin
中科院分区：
文献类型：
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作者：
Guo, Tiantian;Bian, Zichao;Feng, Bin
神经调节作为治疗肠易激综合征(IBS)内脏疼痛的一种非药物替代方案，可能针对远端结肠和直肠(结肠)的敏感型传入，特别是它们在背根神经节(DRG)的胞体。发展选择性背根神经节刺激来控制内脏痛，需要了解结直肠传入胞体的拓扑分布，这些胞体稀疏地分布在DRG中。在这里，我们实现了GCaMP6f来进行高通量光学记录的大肠传入活动在腰臀背根神经节，即光电生理。采用小鼠远端结直肠和L5-S1背根节连续的体外制备方法，记录了791例结直肠传入神经对分级扩张(15、30、40和60 mm Hg)和/或管腔剪切流(20-30 m L/min)的反应，并将其功能分类为4种机械敏感类型，并确定其体节在背根节中的拓扑分布。在791个直肠传入神经节中，L6 DRG占90.8%，S1 DRG占8.3%，L5 DRG仅占0.9%。L6传入有4种类型：粘膜传入占29%，肌肉-粘膜传入占18.4%，低阈值(LT)传入占34%，高阈值(HT)传入占18.2%。S1传入仅有三类：粘膜传入占19.7%，LT肌肉传入占34.8%，HT肌肉传入占45.5%。所有7个L5传入神经均为HT肌肉传入。在L6背根节，HT肌传入的胞体聚集在尾侧区域，而其他类型的胞体不聚集在特定的区域。这项研究的结果可以直接为下一代神经调节设备的设计和改进提供参考，这些设备以DRG为靶点，减轻IBS患者的内脏疼痛。
Neuromodulation as a non-drug alternative for managing visceral pain in irritable bowel syndrome (IBS) may target sensitized afferents of distal colon and rectum (colorectum), especially their somata in the dorsal root ganglion (DRG). Developing selective DRG stimulation to manage visceral pain requires knowledge of the topological distribution of colorectal afferent somata which are sparsely distributed in the DRG. Here, we implemented GCaMP6f to conduct high-throughput optical recordings of colorectal afferent activities in lumbosacral DRG, that is, optical electrophysiology. Using a mouse ex vivo preparation with distal colorectum and L5-S1 DRG in continuity, we recorded 791 colorectal afferents' responses to graded colorectal distension (15, 30, 40, and 60 mmHg) and/or luminal shear flow (20-30 mL/min), then functionally classified them into four mechanosensitive classes, and determined the topological distribution of their somata in the DRG. Of the 791 colorectal afferents, 90.8% were in the L6 DRG, 8.3% in the S1 DRG, and only 0.9% in the L5 DRG. L6 afferents had all four classes: 29% mucosal, 18.4% muscular-mucosal, 34% low-threshold (LT) muscular, and 18.2% highthreshold (HT) muscular afferents. S1 afferents only had three classes: 19.7% mucosal, 34.8% LT muscular, and 45.5% HT muscular afferents. All seven L5 afferents were HT muscular. In L6 DRG, somata of HT muscular afferents were clustered in the caudal region whereas somata of the other classes did not cluster in specific regions. Outcomes of this study can directly inform the design and improvement of next-generation neuromodulation devices that target the DRG to alleviate visceral pain in IBS patients.