Publication

Back to overview

How Gastrin-Releasing Peptide Opens the Spinal Gate for Itch

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Pagani Martina, Albisetti Gioele W., Sivakumar Nandhini, Wildner Hendrik, Santello Mirko, Johannssen Helge C., Zeilhofer Hanns Ulrich,
Project Dorsal Horn Neuronal Circuits Processing Itch
Show all

Original article (peer-reviewed)

Journal Neuron
Volume (Issue) 103(1)
Page(s) 102 - 117.e5
Title of proceedings Neuron
DOI 10.1016/j.neuron.2019.04.022

Open Access

URL http://doi.org/10.1016/j.neuron.2019.04.022
Type of Open Access Publisher (Gold Open Access)

Abstract

Spinal transmission of pruritoceptive (itch) signals requires transneuronal signaling by gastrin-releasing peptide (GRP) produced by a subpopulation of dorsal horn excitatory interneurons. These neurons also express the glutamatergic marker vGluT2, raising the question of why glutamate alone is insufficient for spinal itch relay. Using optogenetics together with slice electrophysiology and mouse behavior, we demonstrate that baseline synaptic coupling between GRP and GRP receptor (GRPR) neurons is too weak for suprathreshold excitation. Only when we mimicked the endogenous firing of GRP neurons and stimulated them repetitively to fire bursts of action potentials did GRPR neurons depolarize progressively and become excitable by GRP neurons. GRPR but not glutamate receptor antagonism prevented this action. Provoking itch-like behavior by optogenetic activation of spinal GRP neurons required similar stimulation paradigms. These results establish a spinal gating mechanism for itch that requires sustained repetitive activity of presynaptic GRP neurons and postsynaptic GRP signaling to drive GRPR neuron output.
-