TY - JOUR
T1 - Cell type-specific modulation of sensory and affective components of itch in the periaqueductal gray
AU - Samineni, Vijay K.
AU - Grajales-Reyes, Jose G.
AU - Sundaram, Saranya S.
AU - Yoo, Judy J.
AU - Gereau, Robert W.
N1 - Funding Information:
This work was funded by NINDS R01NS106953 to RWG, Urology Care Foundation Research Scholars Program and Kailash Kedia Research Scholar award and NIDDK Career development award (K01 DK115634) to VKS, and the Medical Scientist Training Program (MSTP) Grant T32GM07200 and NINDS NRSA 5F31NS103472-02 to JGGR. We thank Christian Pedersen and Michael R Bruchas for their help with Matlab code for the photometry analysis. We thank Sherri Vogt for her assistance with mouse colony maintenance and genotyping. We would like to thank Dr. Steve Davidson, Dr. Judy Golden and Dr. Bryan Copits for helpful discussion with the manuscript and experimental design; we would like to thank all the Gereau lab members for their help with manuscript preparation.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Itch is a distinct aversive sensation that elicits a strong urge to scratch. Despite recent advances in our understanding of the peripheral basis of itch, we know very little regarding how central neural circuits modulate acute and chronic itch processing. Here we establish the causal contributions of defined periaqueductal gray (PAG) neuronal populations in itch modulation in mice. Chemogenetic manipulations demonstrate bidirectional modulation of scratching by neurons in the PAG. Fiber photometry studies show that activity of GABAergic and glutamatergic neurons in the PAG is modulated in an opposing manner during chloroquine-evoked scratching. Furthermore, activation of PAG GABAergic neurons or inhibition of glutamatergic neurons resulted in attenuation of scratching in both acute and chronic pruritis. Surprisingly, PAG GABAergic neurons, but not glutamatergic neurons, may encode the aversive component of itch. Thus, the PAG represents a neuromodulatory hub that regulates both the sensory and affective aspects of acute and chronic itch.
AB - Itch is a distinct aversive sensation that elicits a strong urge to scratch. Despite recent advances in our understanding of the peripheral basis of itch, we know very little regarding how central neural circuits modulate acute and chronic itch processing. Here we establish the causal contributions of defined periaqueductal gray (PAG) neuronal populations in itch modulation in mice. Chemogenetic manipulations demonstrate bidirectional modulation of scratching by neurons in the PAG. Fiber photometry studies show that activity of GABAergic and glutamatergic neurons in the PAG is modulated in an opposing manner during chloroquine-evoked scratching. Furthermore, activation of PAG GABAergic neurons or inhibition of glutamatergic neurons resulted in attenuation of scratching in both acute and chronic pruritis. Surprisingly, PAG GABAergic neurons, but not glutamatergic neurons, may encode the aversive component of itch. Thus, the PAG represents a neuromodulatory hub that regulates both the sensory and affective aspects of acute and chronic itch.
UR - http://www.scopus.com/inward/record.url?scp=85072660737&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-12316-0
DO - 10.1038/s41467-019-12316-0
M3 - Article
C2 - 31554789
AN - SCOPUS:85072660737
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4356
ER -