Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/113585
Title: Adenosine A2A Receptors Shut Down Adenosine A1 Receptor-Mediated Presynaptic Inhibition to Promote Implementation of Hippocampal Long-Term Potentiation
Authors: Lopes, Cátia R. 
Gonçalves, Francisco Q. 
Olaio, Simão 
Tomé, Ângelo R. 
Cunha, Rodrigo A. 
Lopes, João Pedro 
Keywords: adenosine; release; synapse; A1 receptor; A2A receptor; LTP; hippocampus; crosstalk
Issue Date: 21-Apr-2023
Publisher: MDPI
Project: LCF/PR/HP17/52190001 
CENTRO- 01-0145-FEDER-000008 
CENTRO-01-0246-FEDER-000010 
POCI-01- 0145-FEDER-03127 
info:eu-repo/grantAgreement/UIDB/04539/2020 
metadata.degois.publication.title: Biomolecules
metadata.degois.publication.volume: 13
metadata.degois.publication.issue: 4
Abstract: Adenosine operates a modulation system fine-tuning the efficiency of synaptic transmission and plasticity through A1 and A2A receptors (A1R, A2AR), respectively. Supramaximal activation of A1R can block hippocampal synaptic transmission, and the tonic engagement of A1R-mediated inhibition is increased with increased frequency of nerve stimulation. This is compatible with an activity-dependent increase in extracellular adenosine in hippocampal excitatory synapses, which can reach levels sufficient to block synaptic transmission. We now report that A2AR activation decreases A1R-medated inhibition of synaptic transmission, with particular relevance during high-frequency-induced long-term potentiation (LTP). Thus, whereas the A1R antagonist DPCPX (50 nM) was devoid of effects on LTP magnitude, the addition of an A2AR antagonist SCH58261 (50 nM) allowed a facilitatory effect of DPCPX on LTP to be revealed. Additionally, the activation of A2AR with CGS21680 (30 nM) decreased the potency of the A1R agonist CPA (6-60 nM) to inhibit hippocampal synaptic transmission in a manner prevented by SCH58261. These observations show that A2AR play a key role in dampening A1R during high-frequency induction of hippocampal LTP. This provides a new framework for understanding how the powerful adenosine A1R-mediated inhibition of excitatory transmission can be controlled to allow the implementation of hippocampal LTP.
URI: https://hdl.handle.net/10316/113585
ISSN: 2218-273X
DOI: 10.3390/biom13040715
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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