Astrocytic A 2A receptors silencing negatively impacts hippocampal synaptic plasticity and memory of adult mice.

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 A 2A receptors (A 2A R) are a potential candidate to modulate this bidirectional communication, since A 2A R regulate synaptic plasticity and memory and also control key astrocytic functions. Nonetheless, little is known about the role of astrocytic A 2A R in synaptic plasticity and hippocampal-dependent memory. Here, we investigated the impact of genetic silencing astrocytic A 2A R on hippocampal synaptic plasticity and memory of adult mice. The genetic A 2A 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 A 2A R expression in astrocytes of male adult mice carrying "floxed" A 2A R gene, as confirmed by A 2A R binding assays. Astrocytic A 2A 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 A 2A R control astrocytic morphology and influence hippocampal synaptic plasticity and memory of adult mice in a manner different from neuronal A 2A R.