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Caffeine-induced synaptic potentiation in hippocampal CA2 neurons


Caffeine enhances cognition, but even high non-physiological doses have modest effects on synapses. A1 adenosine receptors (A1Rs) are antagonized by caffeine and are most highly enriched in hippocampal CA2, which has not been studied in this context. We found that physiological doses of caffeine in vivo or A1R antagonists in vitro induced robust, long-lasting potentiation of synaptic transmission in rat CA2 without affecting other regions of the hippocampus.

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Figure 1: Orally administered caffeine potentiates synaptic responses in CA2.
Figure 2: A1R antagonists induce a long-lasting increase in synaptic strength in CA2 neurons in vitro.
Figure 3: A1R potentiation at CA2 synapses is mediated by cAMP-dependent activation of PKA.


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We thank D. Armstrong and members of the Dudek laboratory for their input on the manuscript. This research was supported by the Intramural Research Program of the US National Institutes of Health, National Institute of Environmental Health Sciences (Z01 ES 100221).

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S.B.S. and S.M.D. conceived and designed the study. Experiments were conducted and analyzed by S.B.S., D.A.C. and M.Z. S.B.S., D.A.C. and S.M.D. wrote the manuscript. S.M.D. supervised the project.

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Correspondence to Serena M Dudek.

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The authors declare no competing financial interests.

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Simons, S., Caruana, D., Zhao, M. et al. Caffeine-induced synaptic potentiation in hippocampal CA2 neurons. Nat Neurosci 15, 23–25 (2012).

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