Journal Article

Adenosine A<sub>1</sub> Receptor Suppresses Tonic GABA<sub>A</sub> Receptor Currents in Hippocampal Pyramidal Cells and in a Defined Subpopulation of Interneurons

Diogo M. Rombo, Raquel B. Dias, Sofia T. Duarte, Joaquim A. Ribeiro, Karri P. Lamsa and Ana M. Sebastião

in Cerebral Cortex

Volume 26, issue 3, pages 1081-1095
Published in print March 2016 | ISSN: 1047-3211
Published online December 2014 | e-ISSN: 1460-2199 | DOI: http://dx.doi.org/10.1093/cercor/bhu288
Adenosine A1 Receptor Suppresses Tonic GABAA Receptor Currents in Hippocampal Pyramidal Cells and in a Defined Subpopulation of Interneurons

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Adenosine is an endogenous neuromodulator that decreases excitability of hippocampal circuits activating membrane-bound metabotropic A1 receptor (A1R). The presynaptic inhibitory action of adenosine A1R in glutamatergic synapses is well documented, but its influence on inhibitory GABAergic transmission is poorly known. We report that GABAA receptor (GABAAR)-mediated tonic, but not phasic, transmission is suppressed by A1R in hippocampal neurons. Adenosine A1R activation strongly inhibits GABAAR agonist (muscimol)-evoked currents in Cornu Ammonis 1 (CA1) pyramidal neurons and in a specific subpopulation of interneurons expressing axonal cannabinoid receptor type 1. In addition, A1R suppresses tonic GABAAR currents measured in the presence of elevated ambient GABA as well as in naïve slices. The inhibition of GABAergic currents involves both protein kinase A (PKA) and protein kinase C (PKC) signaling pathways and decreases GABAAR δ-subunit expression. On the contrary, no A1R-mediated modulation was detected in phasic inhibitory postsynaptic currents evoked either by afferent electrical stimulation or by spontaneous quantal release. The results show that A1R modulates extrasynaptic rather than synaptic GABAAR-mediated signaling, and that this modulation selectively occurs in hippocampal pyramidal neurons and in a specific subpopulation of inhibitory interneurons. We conclude that modulation of tonic GABAAR signaling by adenosine A1R in specific neuron types may regulate neuronal gain and excitability in the hippocampus.

Keywords: disinhibition; GABAergic interneurons; network excitability; neuromodulation; tonic and phasic inhibition

Journal Article.  10330 words.  Illustrated.

Subjects: Neurology ; Clinical Neuroscience ; Neuroscience

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