Adenosine A2b receptors control A1 receptor-mediated inhibition of synaptic transmission in the mouse hippocampus.
Eur J Neurosci. 2015-02-19; 41(7): 878-888
DOI: 10.1111/ejn.12851
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Adenosine is a neuromodulator mostly acting through A1 (inhibitory) and A2A
(excitatory) receptors in the brain. A2B receptors (A(2B)R) are
G(s/q)–protein-coupled receptors with low expression in the brain. As A(2B)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(2B)R-knockout
(A(2B)R-KO) and C57/BL6 mice were submitted to a behavioural test battery (open
field, elevated plus-maze, Y-maze). The A(2B)R agonist BAY60-6583 (300 nM)
decreased the paired-pulse stimulation ratio, an effect prevented by the A(2B)R
antagonist MRS 1754 (200 nM) and abrogated in A(2B)R-KO mice. Accordingly, A(2B)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 μM) and the disinhibition caused by
the A(1)R antagonist DPCPX (100 nM), both effects prevented by MRS 1754 and
abrogated in A(2B)R-KO mice. BAY 60-6583 decreased glutamate release in slices
and also attenuated the A(1)R inhibition (CPA 100 nM). A(2B)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(2B)R are present in hippocampal
glutamatergic terminals where they counteract the predominant A(1)R-mediated
inhibition of synaptic transmission, impacting on exploratory behaviour.