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ULTRASELECTIVE GRAB SENSORS REVEAL DISTINCT ENDOCANNABINOIDS DYNAMICS IN VIVO<IMG SRC="" CLASS="FR-FIC FR-FIL FR-DIB FR-DRAGGABLE">
Ruyi Caiand 8 co-authors
Peking University
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS07-10AM-017
Presentation
Date TBA
Board: PS07-10AM-017
Event Information
Poster Board
PS07-10AM-017
Poster
View posterAbstract
Endocannabinoids (eCBs), primarily anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are vital retrograde neuromodulators, yet their precise in vivo dynamics remain obscure due to limited detection methods. While our previous sensor, GRABeCB2.0, monitored general eCB activity, it could not distinguish between AEA and 2-AG. To address this, we engineered two selective sensors: GRABAEA2.0 (AEA2.0) and GRAB2-AG2.0 (2-AG2.0). AEA2.0 demonstrates high specificity for AEA with peak fluorescence responses (ΔF/F0) exceeding 1000% and no response to 2-AG. Conversely, 2-AG2.0 responds selectively to 2-AG with ~600% ΔF/F0 without detecting AEA. Using fiber photometry in living mice, we applied these tools to investigate eCB dynamics during stress and drug administration. During foot shock experiments, only 2-AG2.0 revealed specific time-locked signals in the nucleus accumbens core (NAcC) and basolateral amygdala (BLA), with notably slower signal decay in the NAcC. Furthermore, we investigated eCB signaling in the nucleus accumbens shell (NAcSh) during psychoactive drug exposure. We observed distinct release patterns: AEA signals were exclusively triggered by nicotine intake, whereas 2-AG signals were selectively elicited by Δ9-tetrahydrocannabinol (Δ9-THC) administration. These findings underscore the distinct activation of AEA and 2-AG pathways by different addictive substances. In summary, AEA2.0 and 2-AG2.0 provide robust, selective tools for real-time monitoring of specific endocannabinoids, offering critical insights into the complex neuromodulatory roles of the endocannabinoid system.
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