Mesoscale network architecture regulates spontaneous activity
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1
Albert Ludwigs Universität Freiburg, Department of Microsystems Engineering, IMTEK, Germany
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2
Bernstein Zentrum Freiburg, Albert Ludwigs Universität Freiburg, Germany
Spontaneous network activity robustly emerges in developing neuronal networks in vivo and in vitro. The neurophysiological and anatomical requirements for the generation of such activity, however, are poorly understood. Network simulations indicate that clustered connectivity may foster the generation, maintenance and richness of spontaneous activity. Since this mesoscale architecture cannot be systematically modified in living animals, testing these predictions is impracticable in vivo. Here, we investigate how the mesoscale architecture shapes spontaneous activity in developing networks of rat cortical neurons in vitro. In these networks, neurons spontaneously arrange into local clusters with high neurite density and form fasciculating long-range axons. We modified this structure by modulation of protein kinase C, an enzyme regulating neurite growth and cell migration. Inhibition of protein kinase C reduced neuronal aggregation and fasciculation of axons, i.e. promoted uniform architecture. Conversely, activation of protein kinase C promoted aggregation of neurons into clusters, local connectivity and bundling of long-range axons. Supporting predictions from theory, clustered networks were more spontaneously active and generated diverse activity patterns. Neurons within clusters received stronger synaptic inputs and displayed increased membrane potential fluctuations. Intensified clustering promoted the initiation of synchronous bursting events but entailed incomplete network recruitment. Moderately clustered networks appear optimal for initiation and propagation of diverse patterns of activity. Our findings support a crucial role of the mesoscale architectures in the regulation of spontaneous activity dynamics.
Acknowledgements
This work was supported by BrainLinks-BrainTools, Cluster of Excellence funded by the German Research Foundation (Grant EXC 1086), and Bernstein Focus: Neurotechnology Freiburg–Tuebingen (FKZ 01GQ0420).
References
Okujeni S, Kandler S, Egert U (2017) Mesoscale Architecture Shapes Initiation and Richness of Spontaneous Network Activity. J Neurosci 37:3972–3987.
Keywords:
development,
connectivity,
PKC,
spontaneous activity,
in vitro culture
Conference:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays, Reutlingen, Germany, 4 Jul - 6 Jul, 2018.
Presentation Type:
Poster Presentation
Topic:
Neural Networks
Citation:
Okujeni
S and
Egert
U
(2019). Mesoscale network architecture regulates spontaneous activity.
Conference Abstract:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays.
doi: 10.3389/conf.fncel.2018.38.00042
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Received:
17 Mar 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Dr. Samora Okujeni, Albert Ludwigs Universität Freiburg, Department of Microsystems Engineering, IMTEK, Freiburg, Baden Wuerttemberg, 79110, Germany, okujeni@bcf.uni-freiburg.de