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. 2023 Sep;71(9):2137-2153.
doi: 10.1002/glia.24384. Epub 2023 May 15.

Astrocytic A2A receptors silencing negatively impacts hippocampal synaptic plasticity and memory of adult mice

Daniela Madeira  1   2 , Cátia R Lopes  1   2 , Ana P Simões  2 , Paula M Canas  2 , Rodrigo A Cunha  1   2 , Paula Agostinho  1   2
Affiliations

Astrocytic A2A receptors silencing negatively impacts hippocampal synaptic plasticity and memory of adult mice

Daniela Madeira et al. Glia. 2023 Sep.

Abstract

Astrocytes are wired to bidirectionally communicate with neurons namely with synapses, thus shaping synaptic plasticity, which in the hippocampus is considered to underlie learning and memory. Adenosine A2A receptors (A2A R) are a potential candidate to modulate this bidirectional communication, since A2A R regulate synaptic plasticity and memory and also control key astrocytic functions. Nonetheless, little is known about the role of astrocytic A2A R in synaptic plasticity and hippocampal-dependent memory. Here, we investigated the impact of genetic silencing astrocytic A2A R on hippocampal synaptic plasticity and memory of adult mice. The genetic A2A R silencing in astrocytes was accomplished by a bilateral injection into the CA1 hippocampal area of a viral construct (AAV5-GFAP-GFP-Cre) that inactivate A2A R expression in astrocytes of male adult mice carrying "floxed" A2A R gene, as confirmed by A2A R binding assays. Astrocytic A2A R silencing alters astrocytic morphology, typified by an increment of astrocytic arbor complexity, and led to deficits in spatial reference memory and compromised hippocampal synaptic plasticity, typified by a reduction of LTP magnitude and a shift of synaptic long-term depression (LTD) toward LTP. These data indicate that astrocytic A2A R control astrocytic morphology and influence hippocampal synaptic plasticity and memory of adult mice in a manner different from neuronal A2A R.

Keywords: adenosine A2A receptors; astrocytes; hippocampus; memory; synaptic plasticity.

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