Adenosine A2A Receptors Shut Down Adenosine A1 Receptor-Mediated Presynaptic Inhibition to Promote Implementation of Hippocampal Long-Term Potentiation
Open Access
- 21 April 2023
- journal article
- research article
- Published by MDPI AG in Biomolecules
- Vol. 13 (4) , 715
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.Keywords
Funding Information
- La Caixa Foundation (LCF/PR/HP17/52190001, CENTRO-01-0145-FEDER-000008, CENTRO-01-0246-FEDER-000010, POCI-01-0145-FEDER-03127, UIDB/04539/2020)
- Programa Operacional Regional do Centro (LCF/PR/HP17/52190001, CENTRO-01-0145-FEDER-000008, CENTRO-01-0246-FEDER-000010, POCI-01-0145-FEDER-03127, UIDB/04539/2020)
- Fundação para a Ciência e a Tecnologia (LCF/PR/HP17/52190001, CENTRO-01-0145-FEDER-000008, CENTRO-01-0246-FEDER-000010, POCI-01-0145-FEDER-03127, UIDB/04539/2020)
This publication has 84 references indexed in Scilit:
- Functional interaction between pre‐synaptic α6β2‐containing nicotinic and adenosine A2A receptors in the control of dopamine release in the rat striatumBritish Journal of Pharmacology, 2013
- Neuronal adenosine release, and not astrocytic ATP release, mediates feedback inhibition of excitatory activityProceedings of the National Academy of Sciences, 2012
- Adenosine A2A Receptors Are Essential for Long-Term Potentiation of NMDA-EPSCs at Hippocampal Mossy Fiber SynapsesNeuron, 2008
- Capabilities of the WinLTP data acquisition program extending beyond basic LTP experimental functionsJournal of Neuroscience Methods, 2007
- Mice lacking the adenosine A1 receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowlySynapse, 2005
- Involvement of Cannabinoid Receptors in the Regulation of Neurotransmitter Release in the Rodent Striatum: A Combined Immunochemical and Pharmacological AnalysisJournal of Neuroscience, 2005
- Binding of the prototypical adenosine A2A receptor agonist CGS 21680 to the cerebral cortex of adenosine A1 and A2A receptor knockout miceBritish Journal of Pharmacology, 2004
- Modification of adenosine modulation of synaptic transmission in the hippocampus of aged ratsBritish Journal of Pharmacology, 2000
- Synaptic plasticity: LTP and LTDCurrent Opinion in Neurobiology, 1994
- Ecto‐5′‐Nucleotidase Is Associated with Cholinergic Nerve Terminals in the Hippocampus but Not in the Cerebral Cortex of the RatJournal of Neurochemistry, 1992