A subpopulation of projections from the parabrachial nucleus to the central amygdala mediates itch.

Abstract

The parabrachial nucleus (PBN) plays a crucial role in transmitting itch and affective pain signals to the brain regions such as the central amygdala (CeA). While CGRPPBN neurons have been implicated in itch processing, the specific projections involved remain unclear. This study aimed to determine the proportion of itch-responsive PBN-CeA projections that express CGRP and to assess their functional role in itch and anxiety behaviors in mice. Using the Targeted Recombination in Active Populations system, we labeled itch-responsive PBN neurons with serotonin. Retrograde tracing revealed that approximately half of serotonin-responsive PBN neurons projecting to the CeA are CGRP. Optogenetic stimulation of these PBN-CeA neurons elicited scratching behavior but did not enhance pruritogen-induced scratching or affect anxiety-like behaviors. In a mouse model of chronic itch, the inhibition of PBN-CeA neurons significantly reduced spontaneous scratching without impacting anxiety-like behaviors. These findings suggest that serotonin-responsive PBN-CeA neurons include both CGRPand non-CGRPpopulations and selectively mediate itch signaling.