Journal
FRONTIERS IN PHARMACOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2017.00899
Keywords
caffeine; human neocortex; synapses; adenosine; A(1)R; pyramidal neuron
Categories
Funding
- Maratona da Saude
- Santa Casa da Misericordia
- GAI-FMUC
- Banco Santander-Totta
- NARSAD
- Erasmus Mundus Joint Doctorate grant (ENC-Network)
- ERDF, through Centro 2020 [CENTRO-01-0145-FEDER-000008:BrainHealth 2020]
- ERDF, through FCT [POCI-01-0145-FEDER-007440, PTDC/NEU-NMC/4154/2016]
- Netherlands Organization for Scientific Research (NWO
- VICI grant)
- ERC StG BrainSignals
- EU H2020 Framework Programme [604102]
- EU 7th framework program (EU MSCA-ITN CognitionNet) [FP7-PEOPLE-2013-ITN 607508]
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Caffeine is the most widely used psychoactive drug, bolstering attention and normalizing mood and cognition, all functions involving cerebral cortical circuits. Whereas studies in rodents showed that caffeine acts through the antagonism of inhibitory A(1) adenosine receptors (A(1)R), neither the role of A(1)R nor the impact of caffeine on human cortical neurons is known. We here provide the first characterization of the impact of realistic concentrations of caffeine experienced by moderate coffee drinkers (50 mu M) on excitability of pyramidal neurons and excitatory synaptic transmission in the human temporal cortex. Moderate concentrations of caffeine disinhibited several of the inhibitory A(1)R-mediated effects of adenosine, similar to previous observations in the rodent brain. Thus, caffeine restored the adenosine-induced decrease of both intrinsic membrane excitability and excitatory synaptic transmission in the human pyramidal neurons through antagonism of post-synaptic A(1)R. Indeed, the A(1)R-mediated effects of endogenous adenosine were more efficient to inhibit synaptic transmission than neuronal excitability. This was associated with a distinct affinity of caffeine for synaptic versus extra-synaptic human cortical A(1)R, probably resulting from a different molecular organization of A(1)R in human cortical synapses. These findings constitute the first neurophysiological description of the impact of caffeine on pyramidal neuron excitability and excitatory synaptic transmission in the human temporal cortex, providing adequate ground for the effects of caffeine on cognition in humans.
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