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• W1498691251 abstract "ABSTRACT Adenosine inhibits excitatory neurons widely in the brain through adenosine A 1 receptor, but activation of adenosine A 2A receptor (A 2A R) has an opposite effect promoting discharge in neuronal networks. In the hippocampus A 2A R expression level is low, and the receptor's effect on identified neuronal circuits is unknown. Using optogenetic afferent stimulation and whole‐cell recording from identified postsynaptic neurons we show that A 2A R facilitates excitatory glutamatergic Schaffer collateral synapses to CA1 pyramidal cells, but not to GABAergic inhibitory interneurons. In addition, A 2A R enhances GABAergic inhibitory transmission between CA1 area interneurons leading to disinhibition of pyramidal cells. Adenosine A 2A R has no direct modulatory effect on GABAergic synapses to pyramidal cells. As a result adenosine A 2A R activation alters the synaptic excitation ‐ inhibition balance in the CA1 area resulting in increased pyramidal cell discharge to glutamatergic Schaffer collateral stimulation. In line with this, we show that A 2A R promotes synchronous pyramidal cell firing in hyperexcitable conditions where extracellular potassium is elevated or following high‐frequency electrical stimulation. Our results revealed selective synapse‐ and cell type specific adenosine A 2A R effects in hippocampal CA1 area. The uncovered mechanisms help our understanding of A 2A R's facilitatory effect on cortical network activity. © 2014 The Authors Hippocampus Published by Wiley Periodicals, Inc." @default.
• W1498691251 created "2016-06-24" @default.
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• W1498691251 date "2014-11-29" @default.
• W1498691251 modified "2023-10-16" @default.
• W1498691251 title "Synaptic mechanisms of adenosine A _2A receptor‐mediated hyperexcitability in the hippocampus" @default.
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• W1498691251 doi "https://doi.org/10.1002/hipo.22392" @default.
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