Cellular, circuit and transcriptional framework for modulation of itch in the central amygdala.

Vijay K Samineni,Jose G Grajales-Reyes,Edem S Ankudey,Michael R Bruchas,Julian N Sackey,Sienna B Sewell,Robert W Gereau,Christian Pedersen,Gary E Grajales-Reyes,Eric Tycksen,Bryan A Copits

doi:10.7554/elife.68130

Vijay K Samineni, Jose G Grajales-Reyes + Show 9 more

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https://doi.org/10.7554/elife.68130

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Journal: eLife	Publication Date: May 25, 2021
Citations: 24	License type: CC BY 4.0

Affiliation: University of Washington, Seattle University

Abstract

Itch is an unpleasant sensation that elicits robust scratching and aversive experience. However, the identity of the cells and neural circuits that organize this information remains elusive. Here, we show the necessity and sufficiency of chloroquine-activated neurons in the central amygdala (CeA) for both itch sensation and associated aversion. Further, we show that chloroquine-activated CeA neurons play important roles in itch-related comorbidities, including anxiety-like behaviors, but not in some aversive and appetitive behaviors previously ascribed to CeA neurons. RNA-sequencing of chloroquine-activated CeA neurons identified several differentially expressed genes as well as potential key signaling pathways in regulating pruritis. Finally, viral tracing experiments demonstrate that these neurons send projections to the ventral periaqueductal gray that are critical in modulation of itch. These findings reveal a cellular and circuit signature of CeA neurons orchestrating behavioral and affective responses to pruritus in mice.

Highlights

As organisms have evolved, it has been essential that they acquire the means to sense physical and chemical threats in the world around them
We found that chloroquine-TRAPed central amygdala (CeA) neurons send notably dense axonal projections in the ventral periaqueductal gray (Figure 5a–d)
Because the ventral periaqueductal gray (vPAG) has previously been shown to contribute to pruritic behaviors (Gao et al, 2019; Samineni et al, 2019), we focused our functional studies on this CeA!vPAG circuit

Summary

Introduction

It has been essential that they acquire the means to sense physical and chemical threats in the world around them. One such threat detection system is itch, which accompanies unpleasant sensations that evoke strong urges to scratch and promote learned avoidance behavior (Bautista et al, 2014; Han and Dong, 2014; Ikoma et al, 2006; LaMotte et al, 2014). Recent studies have implicated the CeA in the regulation of itch

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