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      Adenosine Differentially Modulates Synaptic Transmission of Excitatory and Inhibitory Microcircuits in Layer 4 of Rat Barrel Cortex

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          Abstract

          Adenosine is considered to be a key regulator of sleep homeostasis by promoting slow-wave sleep through inhibition of the brain's arousal centers. However, little is known about the effect of adenosine on neuronal network activity at the cellular level in the neocortex. Here, we show that adenosine differentially modulates synaptic transmission between different types of neurons in cortical layer 4 (L4) through activation of pre- and/or postsynaptically located adenosine A1 receptors. In recurrent excitatory connections between L4 spiny neurons, adenosine suppresses synaptic transmission through activation of both pre- and postsynaptic A1 receptors. In reciprocal excitatory and inhibitory connections between L4 spiny neurons and interneurons, adenosine strongly suppresses excitatory transmission via activating presynaptic A1 receptors but only slightly suppresses inhibitory transmission via activating postsynaptic A1 receptors. Adenosine has no effect on inhibitory transmission between L4 interneurons. The effect of adenosine is concentration dependent and first visible at a concentration of 1 μM. The effect of adenosine is blocked by the specific A1 receptor antagonist, 8-cyclopentyltheophylline or the nonspecific adenosine receptor antagonist, caffeine. By differentially affecting excitatory and inhibitory synaptic transmission, adenosine changes the excitation–inhibition balance and causes an overall shift to lower excitability in L4 primary somatosensory (barrel) cortical microcircuits.

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          Author and article information

          Journal
          Cereb Cortex
          Cereb. Cortex
          cercor
          Cerebral Cortex (New York, NY)
          Oxford University Press
          1047-3211
          1460-2199
          September 2017
          13 August 2016
          01 September 2018
          : 27
          : 9
          : 4411-4422
          Affiliations
          [1 ] Institute of Neuroscience and Medicine, INM-2, Research Centre Jülich, D-52425 Jülich, Germany
          [2 ] Department of Biology, University of Pennsylvania , Philadelphia, PA 19104, USA
          [3 ] Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University , D-52074 Aachen, Germany
          [4 ] Jülich-Aachen Research Alliance-Brain, Translational Brain Medicine, D-52074 Aachen, Germany
          [5 ]Current address: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3508 AB Utrecht, The Netherlands
          Author notes
          [* ]Address correspondence to Dirk Feldmeyer. Email: d.feldmeyer@ 123456fz-juelich.de ; Guanxiao Qi. Email: g.qi@ 123456fz-juelich.de
          Article
          PMC6433180 PMC6433180 6433180 bhw243
          10.1093/cercor/bhw243
          6433180
          27522071
          15465afc-d7c4-4091-98f4-03afcd3901ab
          © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
          Page count
          Pages: 12
          Funding
          Funded by: DFG research group on Barrel Cortex Function
          Award ID: BaCoFun, Fe 472/4–2
          Funded by: Helmholtz Society
          Award ID: NIMH R01, MH 099544
          Categories
          Original Articles

          barrel cortex,layer 4,A1 receptors,synaptic transmission,adenosine

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