Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 21, Pages -Publisher
MDPI
DOI: 10.3390/ijms232112826
Keywords
CD73; ecto-nucleotidases; adenosine; A(2A) receptors; fear memory; synaptic plasticity; LTP; P2 receptors
Funding
- La Caixa Banking Foundation [LCF/PR/HP17/52190001]
- Fundacao para a Ciencia e Tecnologia (FCT) [POCI-01-0145-FEDER-031274, UIDB/04539/2020]
- Centro 2020 [CENTRO-01-0246-FEDER-000010]
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CD73 plays a key role in the regulation of fear memory and synaptic plasticity in the amygdala, suggesting it as a potential therapeutic target for interfering with abnormal fear-like emotional processing.
Adenosine A(2A) receptors (A(2A)R) control fear memory and the underlying processes of synaptic plasticity in the amygdala. In other brain regions, A(2A)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(2A)R in controlling fear memory and amygdala long-term potentiation (LTP). The bilateral intracerebroventricular injection of the CD73 inhibitor alpha beta-methylene ADP (AOPCP, 1 nmol/ventricle/day) phenocopied the effect of the A(2A)R blockade by decreasing the expression of fear memory, an effect disappearing in CD73-knockout (KO) mice and in forebrain neuronal A(2A)R-KO mice. In the presence of PPADS (20 mu M) to eliminate any modification of ATP/ADP-mediated P2 receptor effects, both AOPCP (100 mu M) and the A(2A)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(2A)R-KO mice and CD73-KO mice. These data indicate a key role of CD73 in the process of A(2A)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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