Adenosine A2b receptors control A1 receptor‐mediated inhibition of synaptic transmission in the mouse hippocampus. (19th February 2015)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: European journal of neuroscience. Volume 41:Number 7(2015:Apr.)
• Page Start: 876
• Page End: 886
• Publication Date: 2015-02-19
• Subjects: Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.12851
• Languages: English
• ISSNs: 0953-816X

Abstract

<abstract abstract-type="main" id="ejn12851-abs-0001"> <title>Abstract</title> <p>Adenosine is a neuromodulator mostly acting through A<sub>1</sub> (inhibitory) and A<sub>2A</sub> (excitatory) receptors in the brain. A<sub>2B</sub> receptors (A<sub>2</sub><sub>B</sub>R) are G<sub>s/q</sub>‐protein‐coupled receptors with low expression in the brain. As A<sub>2</sub><sub>B</sub>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<sub>2</sub><sub>B</sub>R‐knockout (A<sub>2</sub><sub>B</sub>R‐KO) and C57/BL6 mice were submitted to a behavioural test battery (open field, elevated plus‐maze, Y‐maze). The A<sub>2</sub><sub>B</sub>R agonist BAY60‐6583 (300 n<sc>m</sc>) decreased the paired‐pulse stimulation ratio, an effect prevented by the A<sub>2</sub><sub>B</sub>R antagonist MRS 1754 (200 nM) and abrogated in A<sub>2</sub><sub>B</sub>R‐KO mice. Accordingly, A<sub>2</sub><sub>B</sub>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<sub>1</sub>R control of synaptic transmission, both the A<sub>1</sub>R inhibition caused by 2‐chloroadenosine (0.1–1 μ<sc>m</sc>) and the disinhibition caused by the A<sub>1</sub>R antagonist DPCPX (100 n<sc>m</sc>), both effects prevented by MRS 1754 and abrogated in A<sub>2</sub><sub>B</sub>R‐KO mice. BAY 60‐6583 decreased glutamate release in slices and also attenuated the A<sub>1</sub>R inhibition (CPA 100 n<sc>m</sc>). A<sub>2</sub><sub>B</sub>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<sub>2</sub><sub>B</sub>R are present in hippocampal glutamatergic terminals where they counteract the predominant A<sub>1</sub>R‐mediated inhibition of synaptic transmission, impacting on exploratory behaviour.</p> </abstract>