How Gastrin-Releasing Peptide Opens the Spinal Gate for Itch.
Action Potentials
/ physiology
Animals
Behavior, Animal
Female
Gastrin-Releasing Peptide
/ genetics
Immunohistochemistry
Male
Mice
Mice, Transgenic
Neurons
Optogenetics
Potassium Channel Blockers
/ pharmacology
Pruritus
/ genetics
Receptors, Bombesin
/ antagonists & inhibitors
Receptors, Glutamate
/ physiology
Receptors, Presynaptic
/ metabolism
Spinal Cord
/ cytology
GRP receptor
co-transmission
dorsal horn
interneuron
neuropeptide
optogenetics
pruritus
sensory processing
synaptic transmission
volume transmission
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
03 07 2019
03 07 2019
Historique:
received:
25
10
2018
revised:
01
03
2019
accepted:
11
04
2019
pubmed:
20
5
2019
medline:
23
10
2019
entrez:
20
5
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31103358
pii: S0896-6273(19)30379-4
doi: 10.1016/j.neuron.2019.04.022
pmc: PMC6616317
pii:
doi:
Substances chimiques
Grp protein, mouse
0
Potassium Channel Blockers
0
Receptors, Bombesin
0
Receptors, Glutamate
0
Receptors, Presynaptic
0
Gastrin-Releasing Peptide
80043-53-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102-117.e5Subventions
Organisme : European Research Council
ID : 250128
Pays : International
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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