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Dorsal Horn Gastrin-Releasing Peptide Expressing Neurons Transmit Spinal Itch But Not Pain Signals
- Source :
- The Journal of Neuroscience. 39:2238-2250
- Publication Year :
- 2019
- Publisher :
- Society for Neuroscience, 2019.
-
Abstract
- Gastrin-releasing peptide (GRP) is a spinal itch transmitter expressed by a small population of dorsal horn interneurons (GRP neurons). The contribution of these neurons to spinal itch relay is still only incompletely understood, and their potential contribution to pain-related behaviors remains controversial. Here, we have addressed this question in a series of experiments performed inGRP::creandGRP::eGFPtransgenic male mice. We combined behavioral tests with neuronal circuit tracing, morphology, chemogenetics, optogenetics, and electrophysiology to obtain a more comprehensive picture. We found that GRP neurons form a rather homogeneous population of central cell-like excitatory neurons located in lamina II of the superficial dorsal horn. Multicolor high-resolution confocal microscopy and optogenetic experiments demonstrated that GRP neurons receive direct input from MrgprA3-positive pruritoceptors. Anterograde HSV-based neuronal tracing initiated from GRP neurons revealed ascending polysynaptic projections to distinct areas and nuclei in the brainstem, midbrain, thalamus, and the somatosensory cortex. Spinally restricted ablation of GRP neurons reduced itch-related behaviors to different pruritogens, whereas their chemogenetic excitation elicited itch-like behaviors and facilitated responses to several pruritogens. By contrast, responses to painful stimuli remained unaltered. These data confirm a critical role of dorsal horn GRP neurons in spinal itch transmission but do not support a role in pain.SIGNIFICANCE STATEMENTDorsal horn gastrin-releasing peptide neurons serve a well-established function in the spinal transmission of pruritic (itch) signals. A potential role in the transmission of nociceptive (pain) signals has remained controversial. Our results provide further support for a critical role of dorsal horn gastrin-releasing peptide neurons in itch circuits, but we failed to find evidence supporting a role in pain.
- Subjects :
- Male
Nociception
0301 basic medicine
Interneuron
Population
Pain
10050 Institute of Pharmacology and Toxicology
Mice, Transgenic
610 Medicine & health
Optogenetics
Biology
Somatosensory system
03 medical and health sciences
0302 clinical medicine
Interneurons
Gastrin-releasing peptide
medicine
Animals
education
Research Articles
education.field_of_study
Pruritus
General Neuroscience
2800 General Neuroscience
Posterior Horn Cells
Neuronal tracing
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Gastrin-Releasing Peptide
nervous system
570 Life sciences
biology
Brainstem
Neuroscience
hormones, hormone substitutes, and hormone antagonists
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- The Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....008b07ff2fb1426243ef269b14a054b0