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...
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/21/12826 |
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| author | Ana Patrícia Simões Francisco Q. Gonçalves Daniel Rial Samira G. Ferreira João Pedro Lopes Paula M. Canas Rodrigo A. Cunha |
| author_facet | Ana Patrícia Simões Francisco Q. Gonçalves Daniel Rial Samira G. Ferreira João Pedro Lopes Paula M. Canas Rodrigo A. Cunha |
| author_sort | Ana Patrícia Simões |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T19:01:54Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:01:54Z |
| publishDate | 2022-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bf67d92b1f7a47ef9716b399742bc61e2023-11-24T04:57:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211282610.3390/ijms232112826CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A<sub>2A</sub> Receptor-Mediated Control of Fear Memory and Amygdala PlasticityAna Patrícia Simões0Francisco Q. Gonçalves1Daniel Rial2Samira G. Ferreira3João Pedro Lopes4Paula M. Canas5Rodrigo A. Cunha6CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalAdenosine 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.https://www.mdpi.com/1422-0067/23/21/12826CD73ecto-nucleotidasesadenosineA<sub>2A</sub> receptorsfear memorysynaptic plasticity |
| spellingShingle | Ana Patrícia Simões Francisco Q. Gonçalves Daniel Rial Samira G. Ferreira João Pedro Lopes Paula M. Canas Rodrigo A. Cunha CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A<sub>2A</sub> Receptor-Mediated Control of Fear Memory and Amygdala Plasticity International Journal of Molecular Sciences CD73 ecto-nucleotidases adenosine A<sub>2A</sub> receptors fear memory synaptic plasticity |
| title | CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A<sub>2A</sub> Receptor-Mediated Control of Fear Memory and Amygdala Plasticity |
| title_full | CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A<sub>2A</sub> Receptor-Mediated Control of Fear Memory and Amygdala Plasticity |
| title_fullStr | CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A<sub>2A</sub> Receptor-Mediated Control of Fear Memory and Amygdala Plasticity |
| title_full_unstemmed | CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A<sub>2A</sub> Receptor-Mediated Control of Fear Memory and Amygdala Plasticity |
| title_short | CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A<sub>2A</sub> Receptor-Mediated Control of Fear Memory and Amygdala Plasticity |
| title_sort | cd73 mediated formation of extracellular adenosine is responsible for adenosine a sub 2a sub receptor mediated control of fear memory and amygdala plasticity |
| topic | CD73 ecto-nucleotidases adenosine A<sub>2A</sub> receptors fear memory synaptic plasticity |
| url | https://www.mdpi.com/1422-0067/23/21/12826 |
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