Clustered connectivity promotes synchronous burst initiation in vitro

Abstract

Event Abstract Back to Event Clustered connectivity promotes synchronous burst initiation in vitro Samora Okujeni1, 2, 3*, Nila Mönig2, 3, Steffen Kandler1, 2, 3, Oliver Weihberger1, 2 and Ulrich Egert1, 2 1 Albert-Ludwigs University of Freiburg, Bernstein Center Freiburg, Germany 2 Albert-Ludwigs University of Freiburg, Department of Microsystems Engineering, IMTEK, Germany 3 Albert-Ludwigs University of Freiburg, Department of Biology III, Germany Synchronous bursting events (SBE) are widely observed in developing neuronal systems suggesting that the capability to spontaneously initiate these dynamics reflects a crucial intermediate feature of forming networks. Consistently, SBE dynamics similarly and robustly also emerge as the predominant type of activity in networks of cultured neurons in vitro. We speculate that this might hint towards general neuronal mechanisms guiding network self-organization with the aim to establish these dynamics. Interestingly, theoretical models have shown that hierarchical network structures embedding clusters of strongly inter-connected neurons are optimal for initiating and sustaining spontaneous activity (Kaiser 2010) and clustered network structure typically emerges in networks forming in vitro (Kriegstein 1983). We hypothesize that activity-dependent structural plasticity, being a principle driving force of network self-organization, establishes clustered network structures and thereby promotes spontaneous activity levels. Previous studies showed that protein kinase C (PKC) inhibition promotes dendritic outgrowth and arborization (Metzger 2000), and impairs pruning (Kano 1995), linking this protein closely to structural plasticity. To test our hypothesis we thus inhibited PKC in developing networks of cortical neurons in vitro. We show that developmental inhibition of PKC in cortical cell cultures increased dendritic outgrowth, impaired neurite fasciculation and clustering, and abolished network pruning. This resulted in more homogeneous and potentially better connected networks. Consistently, SBEs propagated faster and in more regular wave fronts. Yet, following our hypothesis, SBEs were triggered from fewer sites and at lower rates suggesting that these homogeneous networks embedded fewer SBE initiation zones. We tested if the homogeneous networks were able to support higher SBE rates providing additional input by electrical stimulation. Interestingly, homogeneous networks achieved comparable rates when electrically stimulated compared to the more clustered control networks. This data suggests that activity-dependent structural plasticity promotes network clustering and thereby spontaneous SBE levels during development. Based on recent evidence for a reciprocal scaling between synaptic strength and number of neuronal partners in vitro (Wilson 2007), we propose that locally more confined synaptic targeting within neuronal clusters promotes stronger and more recurrent coupling of neurons. The resulting connectivity structure could thereby more easily amplify spontaneous excitation locally beyond a critical threshold necessary for SBE initiation. In summary, our results indicate that activity-dependent structural plasticity promotes neuronal clustering and thereby the ability of in vitro networks to spontaneously initiate SBEs. We propose that this might reflect a general strategy pursued by neuronal networks to establish this crucial activity pattern during development. Acknowledgements Supported by the German BMBF (FKZ 01GQ0420) and by the EC (NEURO, No. 12788). Keywords: burst, Cluster, connectivity, in vitro, network, Neuron, PKC, structural plasticity Conference: Bernstein Conference 2012, Munich, Germany, 12 Sep - 14 Sep, 2012. Presentation Type: Poster Topic: Other Citation: Okujeni S, Mönig N, Kandler S, Weihberger O and Egert U (2012). Clustered connectivity promotes synchronous burst initiation in vitro. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference 2012. doi: 10.3389/conf.fncom.2012.55.00112 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 Sep 2012; Published Online: 12 Sep 2012. * Correspondence: Mr. Samora Okujeni, Albert-Ludwigs University of Freiburg, Bernstein Center Freiburg, Freiburg, 79104, Germany, okujeni@bcf.uni-freiburg.de 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 Samora Okujeni Nila Mönig Steffen Kandler Oliver Weihberger Ulrich Egert Google Samora Okujeni Nila Mönig Steffen Kandler Oliver Weihberger Ulrich Egert Google Scholar Samora Okujeni Nila Mönig Steffen Kandler Oliver Weihberger Ulrich Egert PubMed Samora Okujeni Nila Mönig Steffen Kandler Oliver Weihberger Ulrich Egert 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.