BRIEF RESEARCH REPORT published: 16 April 2019 doi: 10.3389/fnmol.2019.00091 Edited by: Hermona Soreq, Hebrew University of Jerusalem, Israel Reviewed by: Sebastian Lobentanzer, Goethe-Universität Frankfurt am Main, Germany Deborah Toiber, Ben-Gurion University of the Negev, Israel *Correspondence: Robert A. Mans rmans@georgiasouthern.edu Received: 31 December 2018 Accepted: 25 March 2019 Published: 16 April 2019 Citation: Mans RA, Hinton KD, Payne CH, Powers GE, Scheuermann NL and Saint-Jean M (2019) Cholinergic Stimulation of the Adult Zebrafish Brain Induces Phosphorylation of Glycogen Synthase Kinase-3 β and Extracellular Signal-Regulated Kinase in the Telencephalon. Front. Mol. Neurosci. 12:91. doi: 10.3389/fnmol.2019.00091 Cholinergic Stimulation of the Adult Zebrafish Brain Induces Phosphorylation of Glycogen Synthase Kinase-3 β and Extracellular Signal-Regulated Kinase in the Telencephalon Robert A. Mans *, Kyle D. Hinton, Cicely H. Payne, Grace E. Powers, Nicole L. Scheuermann and Michael Saint-Jean Department of Biology, Georgia Southern University-Armstrong Campus, Savannah, GA, United States The sequencing of the zebrafish genome, the emergence of powerful gene-editing tools, and the development of in vivo imaging techniques have propelled the economical zebrafish into prominence as a biomedical research model. Neurodegenerative disorders with a cholinergic component, such as Alzheimer’s and Parkinson’s diseases, are currently modeled using zebrafish. Still, the utility of zebrafish as a research model will not be fully realized until their neurophysiological properties are thoroughly characterized. In mammals, the coupling of cholinergic receptors to the phosphorylation of glycogen synthase kinase-3 β (GSK3β) and extracellular signal-regulated kinase 1/2 (ERK1/2) is of critical importance to cognitive processes and imparts protection against neuropathogenic events. Similarly, it is known that cholinergic receptors are required for learning and memory in zebrafish and that in vivo activation of cholinergic receptors induces transient changes in evoked synaptic transmission in the telencephalon. However, the intracellular events mediating cholinergic processes in zebrafish have yet to be elucidated. In the current study, an ex vivo drug treatment assay was used to demonstrate that carbachol (CCh)-mediated cholinergic stimulation of the intact adult zebrafish brain induces phosphorylation of GSK3β and ERK1/2 in the zebrafish telencephalon. These findings suggest GSK3β and ERK1/2 may underly cognitive processes in zebrafish. Keywords: acetylcholine receptor (AChR), glycogen synthase kinase (GSK)-3β, extracellular signal-regulate kinase (ERK1/2), telencephalon, cholinergic, zebrafish INTRODUCTION The contributions of cholinergic neurons span widely across the mammalian brain, including critical roles in cortical and hippocampal processing, attention, decision-making, and the encoding and retrieval of memories (Muir et al., 1992; Bartus, 2000; Rogers and Kesner, 2004; Ferreira- Vieira et al., 2016). Alzheimer’s and Parkinson’s diseases, Down syndrome, amyotrophic lateral Frontiers in Molecular Neuroscience | www.frontiersin.org 1 April 2019 | Volume 12 | Article 91