CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A<sub>2A</sub> Receptor-Mediated Control of Fear Memory and Amygdala Plasticity
Adenosine A<sub>2A</sub> receptors (A<sub>2A</sub>R) control fear memory and the underlying processes of synaptic plasticity in the amygdala. In other brain regions, A<sub>2A</sub>R activation is ensured by ATP-derived extracellular adenosine formed by ecto-5′-nuc...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/21/12826 |
| Summary: | Adenosine A<sub>2A</sub> receptors (A<sub>2A</sub>R) control fear memory and the underlying processes of synaptic plasticity in the amygdala. In other brain regions, A<sub>2A</sub>R activation is ensured by ATP-derived extracellular adenosine formed by ecto-5′-nucleotidase or CD73. We now tested whether CD73 is also responsible to provide for the activation of A<sub>2A</sub>R in controlling fear memory and amygdala long-term potentiation (LTP). The bilateral intracerebroventricular injection of the CD73 inhibitor αβ-methylene ADP (AOPCP, 1 nmol/ventricle/day) phenocopied the effect of the A<sub>2A</sub>R blockade by decreasing the expression of fear memory, an effect disappearing in CD73-knockout (KO) mice and in forebrain neuronal A<sub>2A</sub>R-KO mice. In the presence of PPADS (20 μM) to eliminate any modification of ATP/ADP-mediated P2 receptor effects, both AOPCP (100 μM) and the A<sub>2A</sub>R antagonist, SCH58261 (50 nM), decreased LTP magnitude in synapses of projection from the external capsula into the lateral amygdala, an effect eliminated in slices from both forebrain neuronal A<sub>2A</sub>R-KO mice and CD73-KO mice. These data indicate a key role of CD73 in the process of A<sub>2A</sub>R-mediated control of fear memory and underlying synaptic plasticity processes in the amygdala, paving the way to envisage CD73 as a new therapeutic target to interfere with abnormal fear-like emotional processing. |
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| ISSN: | 1661-6596 1422-0067 |