A Neural Circuit for Modular Gating of Organ Somatosensation
Zhang, Y.; Liu, F.; Yang, L.; Hahm, H.; Heitmeier, M. R.; Okuda, T.; Kawatani, M.; Harrigan, J. T.; Morrison-Rodriguez, E. C.; Petukhova, A.; Lu, Z.; Heitmeier, H. A.; Samineni, V. K.
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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 Trpc4 expression that gate bladder sensory input and regulate micturition reflexes. Single-cell transcriptomics and in situ physiology reveal molecularly distinct Trpc4 subtypes. Functional manipulation reveals that Trpc4 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 Trpc4 neurons. These findings establish Trpc4 interneurons are critical for bladder sensory-motor integration and extend classical spinal gating models to encompass visceral pain and organ reflex control.
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