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Adenosine A 2b receptors control A 1 receptor‐mediated inhibition of synaptic transmission in the mouse hippocampus
Author(s) -
Gonçalves Francisco Q.,
Pires Johny,
Pliassova Anna,
Beleza Rui,
Lemos Cristina,
Marques Joana M.,
Rodrigues Ricardo J.,
Canas Paula M.,
Köfalvi Attila,
Cunha Rodrigo A.,
Rial Daniel
Publication year - 2015
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12851
Subject(s) - glutamate receptor , neurotransmission , adenosine , receptor , excitatory postsynaptic potential , medicine , endocrinology , hippocampal formation , glutamatergic , agonist , stimulation , biology , hippocampus , chemistry , neuroscience , inhibitory postsynaptic potential
Abstract Adenosine is a neuromodulator mostly acting through A 1 (inhibitory) and A 2A (excitatory) receptors in the brain. A 2B receptors (A 2 B R ) are G s/q ‐protein‐coupled receptors with low expression in the brain. As A 2 B R function is largely unknown, we have now explored their role in the mouse hippocampus. We performed electrophysiological extracellular recordings in mouse hippocampal slices, and immunological analysis of nerve terminals and glutamate release in hippocampal slices and synaptosomes. Additionally, A 2 B R ‐knockout (A 2 B R ‐ KO ) and C57/ BL 6 mice were submitted to a behavioural test battery (open field, elevated plus‐maze, Y‐maze). The A 2 B R agonist BAY 60‐6583 (300 n m ) decreased the paired‐pulse stimulation ratio, an effect prevented by the A 2 B R antagonist MRS 1754 (200 nM ) and abrogated in A 2 B R ‐ KO mice. Accordingly, A 2 B R immunoreactivity was present in 73 ± 5% of glutamatergic nerve terminals, i.e. those immunopositive for vesicular glutamate transporters. Furthermore, BAY 60‐6583 attenuated the A 1 R control of synaptic transmission, both the A 1 R inhibition caused by 2‐chloroadenosine (0.1–1 μ m ) and the disinhibition caused by the A 1 R antagonist DPCPX (100 n m ), both effects prevented by MRS 1754 and abrogated in A 2 B R ‐ KO mice. BAY 60‐6583 decreased glutamate release in slices and also attenuated the A 1 R inhibition ( CPA 100 n m ). A 2 B R ‐ KO mice displayed a modified exploratory behaviour with an increased time in the central areas of the open field, elevated plus‐maze and the Y‐maze and no alteration of locomotion, anxiety or working memory. We conclude that A 2 B R are present in hippocampal glutamatergic terminals where they counteract the predominant A 1 R‐mediated inhibition of synaptic transmission, impacting on exploratory behaviour.