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

Proc Natl Acad Sci U S A. 2019 Dec 26;116(52):27011-27017. doi: 10.1073/pnas.1905658116. Epub 2019 Dec 5.

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+ neuron-dependent 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.

Keywords: galanin+ GABAergic neurons; gating itch processing; inhibitory control; rostral ventromedial medulla; spinal GRPR+ neurons.