Keller Jason A, Chen Jingyi, Simpson Sierra, Wang Eric Hou-Jen, Lilascharoen Varoth, George Olivier, Lim Byung Kook, Stowers Lisa
Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
Neurosciences Graduate Program, University of California San Diego, La Jolla, CA, USA.
Nat Neurosci. 2018 Sep;21(9):1229-1238. doi: 10.1038/s41593-018-0204-3. Epub 2018 Aug 13.
Voluntary urination ensures that waste is eliminated when safe and socially appropriate, even without a pressing urge. Uncontrolled urination, or incontinence, is a common problem with few treatment options. Normal urine release requires a small region in the brainstem known as Barrington's nucleus (Bar), but specific neurons that relax the urethral sphincter and enable urine flow are unknown. Here we identify a small subset of Bar neurons that control the urethral sphincter in mice. These excitatory neurons express estrogen receptor 1 (Bar), project to sphincter-relaxing interneurons in the spinal cord and are active during natural urination. Optogenetic stimulation of Bar neurons rapidly initiates sphincter bursting and efficient voiding in anesthetized and behaving animals. Conversely, optogenetic and chemogenetic inhibition reveals their necessity in motivated urination behavior. The identification of these cells provides an expanded model for the control of urination and its dysfunction.
自主排尿确保在安全且符合社会规范的情况下排出废物，即使没有强烈的排尿冲动。不受控制的排尿，即尿失禁，是一个常见问题，治疗选择很少。正常的尿液排出需要脑干中一个称为巴林顿核（Bar）的小区域，但放松尿道括约肌并使尿液排出的特定神经元尚不清楚。在这里，我们在小鼠中鉴定出一小部分控制尿道括约肌的Bar神经元。这些兴奋性神经元表达雌激素受体1（Bar），投射到脊髓中使括约肌放松的中间神经元，并在自然排尿时活跃。对Bar神经元进行光遗传学刺激可在麻醉和清醒的动物中迅速引发括约肌阵发性收缩并有效排尿。相反，光遗传学和化学遗传学抑制揭示了它们在有动机的排尿行为中的必要性。这些细胞的鉴定为排尿控制及其功能障碍提供了一个扩展模型。
