Adenosine receptors are the on-and-off switch of astrocytic cannabinoid type 1 (CB1) receptor effect upon synaptic plasticity in the medial prefrontal cortex

The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A and A receptors (AR, AR), be...

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Detalles Bibliográficos
Autores: Gonçalves-Ribeiro, J., Savchak, O.K., Costa Pinto, P., Gomes, J. I., Rivas-Santisteban, R., Lillo, A., Sánchez Romero, Javier, Sebastião, A.M., Navarrete, Marta, Navarro, Gabriel, Franco, R., Vaz, Sandra
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/377645
Acceso en línea:http://hdl.handle.net/10261/377645
Access Level:acceso abierto
Palabra clave:CB1 receptor
adenosine receptors
astroglia
mPFC
synaptic plasticity.
Descripción
Sumario:The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A and A receptors (AR, AR), being unknown the crosstalk between CB1R and adenosine receptors in these cells. We show here that a further level of regulation of astrocyte Ca signaling occurs through CB1R-AR or CB1R-AR heteromers that ultimately impact mPFC synaptic plasticity. CB1R-mediated Ca transients increased and decreased when AR and AR were activated, 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 AR but not of AR. Notably, in IP3R2KO mice, that do not show astrocytic Ca level elevations, CB1R activation decreases LTP, which is not modified by AR or AR. The present work suggests that CB1R has a homeostatic role on mPFC LTP, under the control of AR, probably due to physical crosstalk between these receptors in astrocytes that ultimately alters CB1R Ca signaling.