Differential cholinergic and serotonergic neuromodulation of network activity in the mouse medial prefrontal cortex

Abstract

Event Abstract Back to Event Differential cholinergic and serotonergic neuromodulation of network activity in the mouse medial prefrontal cortex Maximilian Zeidler1*, Miodrag Mitric2, Kai Kummer2 and Michaela Kress2 1 Innsbruck Medical University, Department für Physiology and Medical Biophysics, Austria 2 Innsbruck Medical University, Department of Physiology and Medical Biophysics, Austria Introduction The medial prefrontal cortex (mPFC) is well known for its prominent role in in decision-making, reward-guided learning and memory formation. It receives dense input from cholinergic neurons originating in the basal forebrain and laterodorsal tegmental nucleus and mPFC neurons express nicotinic as well as muscarinic acetylcholine receptors. In addition, serotonergic neurons emanating from the medial and dorsal raphe nuclei project to various subregions of the PFC and both metabotropic and ionotropic serotonin (5-HT) receptors are expressed in cortical neurons. The actions of both neuromodulators on the mPFC are diverse and insufficiently well understood. Although single cell patch clamp is routinely used to study the role of cholinergic and serotonergic neurons in cortical networks, we provide here first insights in the potential of multielectrode array (MEA) recordings in slices as an efficient and fast screening tool to investigate the neurotransmitters and synaptic modulators on the entire mPFC network. Methods We recorded spontaneous and chemically induced network activity in acute mPFC brain slices with a thickness of 300µm obtained from 10-12 weeks old C57BL/6J mice. After cutting, slices were stored for 12 min in protective-N-methyl-D-glucamine artificial cerebrospinal fluid solution, followed by recovery in artificial cerebrospinal fluid (aCSF) for 45 min. In vitro MEA recordings were performed to assess baseline discharge activity as well as dose specific responses to carbachol (CCh 1µM, 5µM, 25µM, 50µM, 100µM) or 5-HT (doses: 1µM, 50µM, 100µM, 250µM, 500µM) administration to the bath solution. Both, mean spike frequency and the number of activated electrodes were analyzed and dose response curves, time course of activation as well as the net modulatory effect on network activity in the mPFC were compared. In addition, RT-qPCR data were obtained to identify expression levels of cholinergic receptors in the mPFC. Results Recordings revealed a generally low baseline discharge rate with a minority of electrodes showing spontaneous discharge activity. Exposure to CCh induced a significantly enhanced network activity at doses > 5 µM, indicated by a dose-dependent increase in mean spike frequency and a significantly higher number of active electrodes compared to baseline activity. By contrast, 5-HT modulated the activity in the mPFC in a U-shaped dose dependent manner with the highest mean spike frequency after administration of 10µM and 500µM. Although administration of 10µM, 250µM and 500µM of 5-HT showed excitatory effects the mean spike frequency and also the number of activated electrodes was significantly lower compared to CCh stimulation. Conclusion MEA recordings revealed excitatory effects of both CCh and 5-HT in the mPFC. The impact of cholinergic stimulation exceeded serotonergic excitatory effects. Our results support the potential of MEA recordings as an efficient and fast screening technology to assess neuromodulator effects on network activity in acute cortical brain slices. Keywords: neuronal networks, network activity, 5-HT, Acetylcholine, mPFC, Multielectrode array (MEA), acute brain slice, Neuromodulation Conference: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays, Reutlingen, Germany, 4 Jul - 6 Jul, 2018. Presentation Type: Poster Presentation Topic: Stimulation strategies Citation: Zeidler M, Mitric M, Kummer K and Kress M (2019). Differential cholinergic and serotonergic neuromodulation of network activity in the mouse medial prefrontal cortex. Conference Abstract: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays. doi: 10.3389/conf.fncel.2018.38.00055 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 18 Mar 2018; Published Online: 17 Jan 2019. * Correspondence: Mr. Maximilian Zeidler, Innsbruck Medical University, Department für Physiology and Medical Biophysics, Innsbruck, Austria, maximilian.zeidler@student.i-med.ac.at Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Maximilian Zeidler Miodrag Mitric Kai Kummer Michaela Kress Google Maximilian Zeidler Miodrag Mitric Kai Kummer Michaela Kress Google Scholar Maximilian Zeidler Miodrag Mitric Kai Kummer Michaela Kress PubMed Maximilian Zeidler Miodrag Mitric Kai Kummer Michaela Kress Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.