Gonçalves-Ribeiro, JoanaSavchak, Oksana K.Costa-Pinto, SaraGomes, Joana I.Rivas‐Santisteban, RafaelLillo, AlejandroSánchez Romero, JavierSebastião, Ana M.Navarrete, MartaNavarro Brugal, GemmaFranco Fernández, RafaelVaz, Sandra H.2025-02-032025-02-032024-060894-1491https://hdl.handle.net/2445/218451The medial prefrontal cortex (mPFC) is involved in cognitive functions such as work- ing memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca2+) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A1 and A2A receptors (A1R, A2AR), being unknown the cross- talk between CB1R and adenosine receptors in these cells. We show here that a fur- ther level of regulation of astrocyte Ca2+ signaling occurs through CB1R-A2AR or CB1R-A1R heteromers that ultimately impact mPFC synaptic plasticity. CB1R- mediated Ca2+ transients increased and decreased when A1R and A2AR were acti- vated, respectively, unveiling adenosine receptors as modulators of astrocytic CB1R. CB1R activation leads to an enhancement of long-term potentiation (LTP) in the mPFC, under the control of A1R but not of A2AR. Notably, in IP3R2KO mice, that do not show astrocytic Ca2+ level elevations, CB1R activation decreases LTP, which is not modified by A1R or A2AR. The present work suggests that CB1R has a homeo- static role on mPFC LTP, under the control of A1R, probably due to physical crosstalk between these receptors in astrocytes that ultimately alters CB1R Ca2+ signaling.21 p.application/pdfengcc-by-nc-nd (c) Gonçalves-Ribeiro, Joana et al., 2024http://creativecommons.org/licenses/by-nc-nd/3.0/es/AdenosinaAstròcitsAdenosineAstrocytesinfo:eu-repo/semantics/article7529812025-02-03info:eu-repo/semantics/openAccess