Nicotinic effects on physiology and cognitive processes

Cellular and synaptic mechanisms of nicotinic actions on cortical circuits Huib Mansvelder Department Integrative , Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands Most of what we know about cellular mechanisms of nicotinic modulation of cortical processing comes from research on brain. Little is known about whether principles of cholinergic modulation translate to human cortical circuits. In this talk I will discuss how activation of nicotinic acetylcholine receptors alter short and long-term processing by neocortical circuits in human brain in a layer specific manner. Obermayer J, Heistek TS, Kerkhofs A, Goriounova NA, Kroon T, Baayen JC, Idema S, Testa- Silva G, Couey JJ, Mansvelder HD. (2018) Lateral inhibition by Martinotti interneurons is facilitated by cholinergic inputs in human and mouse neocortex. Nature Commun. 2018 Oct 5;9(1):4101. doi: 10.1038/s41467-018-06628-w. Poorthuis RB, Muhammad K, Wang M, Verhoog MB, Junek S, Wrana A, Mansvelder HD, Letzkus JJ. (2018) Rapid of Layer 1 Interneurons in Human Neocortex. Cell Reports. 2018 Apr 24;23(4):951-958. doi: 10.1016/j.celrep.2018.03.111.

Nicotinic impact on and memory formation in Michael A. Nitsche Department of Psychology and , Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund, Dortmund, Germany Recent research in healthy humans has shown that nicotine has a relevant, but complex impact on cortical excitability, neuroplasticity, and associated cognitive functions, including working and long term memory. This talk will deliver mechanistic insights in these effects, and propose a model on how nicotine affects respective functions, including the effect of nicotine on brain physiology and cognition in smokers and non-smokers. Grundey J, Barlay J, Batsikadze G, Kuo MF, Paulus W, Nitsche M. Nicotine modulates human brain plasticity via calcium-dependent mechanisms. J Physiol. 2018 Nov;596(22):5429-5441. Grundey J, Amu R, Batsikadze G, Paulus W, Nitsche MA. Diverging effects of nicotine on motor learning performance: Improvement in deprived smokers and attenuation in non- smokers. Addict Behav. 2017 Nov;74:90-97.

Nicotinic modulation of attention in the human brain Christiane Thiel Department of Psychology, University of Oldenburg, Oldenburg, Germany The talk will give an overview of pharmacological fMRI studies that used nicotine to modulate visuospatial attention and cognitive control in healthy nonsmokers. Nicotine mainly impacts on visuospatial orienting and response speed. Neural signatures are a reduction of BOLD activity in several brain regions, including parietal and frontal cortices and overall changes in brain network topology enabling faster information transfer. I will further point out that there is interindividual variability with respect to the effects of nicotine and that variations in dopaminergic may play an important role. Ahrens, S. & Thiel, C.M. (2020) Effects of Nicotine on Task Switching and Distraction in Non-smokers. An fMRI Study. , 444, 43-53. Giessing, C., Thiel, C.M., Alexander-Bloch, A.F., Patel, A.X. & Bullmore, E.T. (2013) Human brain functional network changes associated with enhanced and impaired attentional task performance. J Neurosci, 33, 5903-5914.

Nicotinic impact on neuroplasticity in patients with Alkomiet Hasan Department of , Psychotherapy, and Psychosomatic, University of Augsburg, Augsburg, Germany The association between impairments in the cholinergic system, plasticity dysfunction and schizophrenia is evident from theoretical and preclinical studies. However, limited evidence from human research is available. The talk will present findings from several experiments with and without manipulation of nAchR in patients with schizophrenia focussing on human motor-cortical plasticity and excitability. de Miquel C, Pross B, Papazova I, Güler D, Hasan A (2020) The two-way relationship between nicotine and cortical activity: a systematic review of neurobiological and treatment aspects. Eur Arch Psychiatry Clin Neurosci. 2020 Jun Strube W, Bunse T, Nitsche MA, Wobrock T, Aborowa R, Misewitsch K, Herrmann M, Falkai P, Hasan A. Smoking restores impaired LTD-like plasticity in schizophrenia: a transcranial direct current stimulation study. Neuropsychopharmacology. 2015 Mar;40(4):822-30