Tac1-expressing neurons in the central amygdala predominantly mediate histamine-induced itch by receiving inputs from parabrachial Tac1-expressing neurons

Itch is a distinct and bothersome sensation closely associated with a strong urge to scratch. Both the parabrachial nucleus (PBN) and the central amygdala (CeA) are responsive to itch stimuli and contain neurons that express tachykinin 1 (Tac1), which are known for their significant involvement in itch-induced scratching at both spinal and supraspinal levels. Significantly, the PBN neurons project their axons to form close connections with the CeA neurons. However, the role of the PBN ^Tac1 -CeA ^Tac1 pathway in modulating itch remains to be determined. We utilized immunohistochemistry, fiber photometry, chemogenetic, and behavioral techniques to investigate the role of the PBN ^Tac1 -CeA ^Tac1 pathway in itch. Our results indicate that neurons in the CeA can be more activated by acute itch than chronic itch. Notably, in response to acute itch stimuli, both CeA ^Tac1 and PBN ^Tac1 neurons are specifically activated by histamine (His)-induced itch. Furthermore, the Tac1-positive terminals from the PBN ^Tac1 neurons formed close connections with CeA ^Tac1 neurons. We also demonstrated that activating the PBN-CeA pathway using a chemogenetic approach could increase scratching behaviors in His-induced itch, other than chloroquine (CQ)-induced itch. Conversely, inhibiting the PBN-CeA pathway decreased scratching behaviors in mice with His-induced itch. Taken together, these results suggest that the PBN ^Tac1 -CeA ^Tac1 pathway may play a specific role in modulating His-induced acute itch.