Synaptic control of spinal GRPR+ neurons by local and long-range inhibitory inputs

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Abstract

Spinal gastrin-releasing peptide receptor-expressing (GRPR+) neurons play an essential role in itch signal processing. However, the circuit mechanisms underlying the modulation of spinal GRPR+ neurons by direct local and long-range inhibitory inputs remain elusive. Using viral tracing and electrophysiological approaches, we dissected the neural circuits underlying the inhibitory control of spinal GRPR+ neurons. We found that spinal galanin+ GABAergic neurons form inhibitory synapses with GRPR+ neurons in the spinal cord and play an important role in gating the GRPR+ neurondependent itch signaling pathway. Spinal GRPR+ neurons also receive inhibitory inputs from local neurons expressing neuronal nitric oxide synthase (nNOS). Moreover, spinal GRPR+ neurons are gated by strong inhibitory inputs from the rostral ventromedial medulla. Thus, both local and long-range inhibitory inputs could play important roles in gating itch processing in the spinal cord by directly modulating the activity of spinal GRPR+ neurons.

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Liu, M. Z., Chen, X. J., Liang, T. Y., Li, Q., Wang, M., Zhang, X. Y., … Sun, Y. G. (2019). Synaptic control of spinal GRPR+ neurons by local and long-range inhibitory inputs. Proceedings of the National Academy of Sciences of the United States of America, 116(52), 27011–27017. https://doi.org/10.1073/pnas.1905658116

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