{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:10:27Z","timestamp":1790745027426,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG grant NI 683\/4\u20102"],"award-info":[{"award-number":["DFG grant NI 683\/4\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>Nicotine (NIC) modulates cognition and memory function by targeting the nicotinic ACh receptor and releasing different transmitter systems postsynaptically.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>With both NIC\u2010generated mechanisms, calcium influx and calcium permeability can be regulated, which is a key requirement for the induction of long\u2010term potentiation, comprising the physiological basis of learning and memory function.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>We attempt to unmask the underlying mechanism of nicotinic effects on anodal transcranial direct current stimulation (tDCS)\u2010induced long\u2010term potentiation\u2010like plasticity based on the hypothesis of calcium\u2010dependency.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Abolished tDCS\u2010induced neuroplasticity as a result of NIC administration is reversed by calcium channel blockade with flunarizine in a dose\u2010dependent manner.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>The results of the present study suggest that there is a dose determination of NIC\/NIC agonists in therapeutical settings when treating cognitive dysfunction, which partially explains the heterogeneous results on cognition observed in subjects in different experimental settings.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Nicotine (NIC) modulates neuroplasticity and improves cognitive performance in animals and humans mainly by increased calcium permeability and modulation of diverse transmitter systems. NIC administration impairs calcium\u2010dependent plasticity induced by non\u2010invasive brain stimulation with transcranial direct current stimulation (tDCS) in non\u2010smoking participants probably as a result of intracellular calcium overflow. To test this hypothesis, we analysed the effect of calcium channel blockade with flunarizine (FLU) on anodal tDCS\u2010induced cortical excitability changes in healthy non\u2010smokers under NIC. We applied anodal tDCS combined with NIC patch and FLU at three different doses (2.5, 5 and 10\u00a0mg) or with placebo medication. NIC abolished anodal tDCS\u2010induced neuroplasticity. Under medium dosage (but not under low and high dosage) of FLU combined with NIC, plasticity was re\u2010established. For FLU alone, the lowest dosage weakened long\u2010term potentiation (LTP)\u2010like plasticity, whereas the highest dosage again abolished tDCS\u2010induced plasticity. The medium dosage turned LTP\u2010like plasticity in long\u2010term depression\u2010like plasticity. The results of the present study suggest a key role of calcium influx and calcium levels in nicotinic effects on LTP\u2010like plasticity in humans. This knowledge might be relevant for the development of new therapeutic strategies in cognitive dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp276502","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T13:13:28Z","timestamp":1537103608000},"page":"5429-5441","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Nicotine modulates human brain plasticity via calcium\u2010dependent mechanisms"],"prefix":"10.1113","volume":"596","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2901-4337","authenticated-orcid":false,"given":"Jessica","family":"Grundey","sequence":"first","affiliation":[{"name":"Department of Clinical Neurophysiology University Medical Center, Georg\u2010August\u2010University G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerick","family":"Barlay","sequence":"additional","affiliation":[{"name":"Department of Clinical 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