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Axonal anisotropy and connectivity inhomogeneities in 2D networks

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Abstract

Cultured neuronal networks are an interesting experimental model in which neurons are freed from cortical architecture and plated on microelectrode arrays (MEA). Present in their dynamics are periods of strongly synchronized spiking by the network, termed 'bursting', whose role is not understood but dominates network dynamics and, due to its resistance to attempts to remove it [1], has been suggested to be an inherent feature in their dynamics. Bursts have been demonstrated to contains distinct spatiotemporal motifs, repudiating the possibility that they are random or chaotic activity. However, the speeds of these propagating wavefronts has been measured as 5-100mm/s [2], and hence much faster than can be accounted for by local connectivity [3]. In attempting to represent cultured networks using 2D network models, typical connectivity models, such as small-world, prove to be insufficient for recreating some of the distinct phenomena associated with the dynamics of cultured networks, noticeably the fast propagation speeds. Here, we introduce a simple but biologically plausible connectivity model that is able to reproduce this phenomena. We extend it to incorporate some of the subtle structural inhomogeneities observed experimentally to investigate their implications for network dynamics. We demonstrate that these inhomogeneities strongly facilitate the propagation of activity as well as being responsible for emergence of distinct burst motifs. Importantly, our model confirms that bursts are indeed an inherent feature of such networks, as they are an inescapable by-product of network connectivity and structure.
P O S T E R P R E S E N T A T I O N Open Access
Axonal anisotropy and connectivity
inhomogeneities in 2D networks
Sarah Jarvs
1,2,3*
, Samora Okujeni
1,2,3
, Steffen Kandler
1,2,3
, Stefan Rotter
1,2
, Ulrich Egert
1,3
From Twenty First Annual Computational Neuroscience Meeting: CNS*2012
Decatur, GA, USA. 21-26 July 2012
Cultured neuronal networks are an interesting experi-
mental model in which neurons are freed from cortical
architecture and plated on microelectrode arrays (MEA).
Present in their dynamics are periods of strongly syn-
chronized spiking by the network, termed bursting,
whose role is not understood but dominates network
dynamics and, due to its resistance to attempts to remove
it [1], has been suggested to be an inherent feature in
their dynamics. Bursts have been demonstrated to con-
tains distinct spatiotemporal motifs, repudiating the pos-
sibility that they are random or chaotic activity. However,
the speeds of these propagating wavefronts has been
measured as 5-100mm/s [2], and hence much faster than
can be accounted for by local connectivity [3].
In attempting to represent cultured networks using 2D
network models, typical connectivity models, such as
small-world, prove to be insufficient for recreating some
of the distinct phenomena associated with the dynamics
of cultured networks, noticeably the fast propagation
speeds.
Here, we introduce a simple but biologically plausible
connectivity model that is able to reproduce this phenom-
ena. We extend it to incorporate some of the subtle struc-
tural inhomogeneities observed experimentally to
investigate their implications for network dynamics. We
demonstrate that these inhomogeneities strongly facilitate
the propagation of activity as well as being responsible for
emergence of distinct burst motifs. Importantly, our
model confirms that bursts are indeed an inherent feature
of such networks, as they are an inescapable by-product of
network connectivity and structure.
Acknowledgements
This work was supported by the German BMBF (FKZ 01GQ0420) and by the
EC (NEURO, No. 12788).
Author details
1
Bernstein Center Freiburg, University of Freiburg, Freiburg, 79104, Germany.
2
Faculty of Biology, University of Freiburg, Freiburg, 79104, Germany.
3
Department of Biomicrotechnology, IMTEK, University of Freiburg, Freiburg,
79096, Germany.
Published: 16 July 2012
References
1. Madhavan R, Chao ZC, Wagenaar DA, Bakkum DJ, Potter SM: Multi-site
stimulation quiets network-wide spontaneous bursts and enhances
functional plasticity in cultured cortical networks. Conf Proc IEEE Eng Med
Biol Soc 2006, 1:1593-1596.
2. Maeda E, Robinson HP, Kawana A: The mechanisms of generation and
propagation of synchronized bursting in developing networks of cortical
neurons. J Neurosci 1995, 15:6834-6845.
3. Kitano K, Fukai T: Variability vs synchronicity of neuronal activity in local
cortical network models with different wiring topologoes. J Comput
Neurosci 2007, 23:237-250.
doi:10.1186/1471-2202-13-S1-P145
Cite this article as: Jarvs et al.: Axonal anisotropy and connectivity
inhomogeneities in 2D networks. BMC Neuroscience 2012 13(Suppl 1):
P145.
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* Correspondence: jarvis@bcf.uni-freiburg.de
1
Bernstein Center Freiburg, University of Freiburg, Freiburg, 79104, Germany
Full list of author information is available at the end of the article
Jarvs et al.BMC Neuroscience 2012, 13(Suppl 1):P145
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The characteristics and mechanisms of synchronized firing in developing networks of cultured cortical neurons were studied using multisite recording through planar electrode arrays (PEAs). With maturation of the network (from 3 to 40 d after plating), the frequency and propagation velocity of bursts increased markedly (approximately from 0.01 to 0.5 Hz and from 5 to 100 mm/sec, respectively), and the sensitivity to extracellular magnesium concentration (0–10 mM) decreased. The source of spontaneous bursts, estimated from the relative delay of onset of activity between electrodes, varied randomly with each burst. Physical separation of synchronously bursting networks into several parts using an ultraviolet laser, divided synchronous bursting into different frequencies and phases in each part. Focal stimulation through the PEA was effective at multiple sites in eliciting bursts, which propagated over the network from the site of stimulation. Stimulated bursts exhibited both an absolute refractory period and a relative refractory period, in which partially propagating bursts could be elicited. Periodic electrical stimulation (at 1 to 30 sec intervals) produced slower propagation velocities and smaller numbers of spikes per burst at shorter stimulation intervals. These results suggest that the generation and propagation of spontaneous synchronous bursts in cultured cortical neurons is governed by the level of spontaneous presynaptic firing, by the degree of connectivity of the network, and by a distributed balance between excitation and recovery processes.
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We culture high-density cortical cultures on multi-electrode arrays (MEAs), which allow us to stimulate and record from thousands of neurons. One of the modes of activity in these high-density cultures is dish-wide synchronized bursting. Unlike in vivo, these synchronized patterns persist for the lifetime of the culture. Such aberrant patterns of activity might be due to the fact that cortical cultures are sensory-deprived and arrested in development. We have devised methods to control this spontaneous activity by multi-electrode electrical stimulation and to study long-term functional neural plasticity, on a background of such burst-quieting stimulation. Here, we investigate whether burst quieting reveals long-term plasticity induced by tetanic stimulation. Spatio-temporal activity patterns (STAPs) that result from probe pulses were clustered and quantified in quieted and non-quieted cultures. Burst-quieted cultures show more tetanus-induced functional change than cultures which are allowed to express spontaneous bursts. The methods developed for this study will help in the understanding of network dynamics and appreciation of their role in long-term plasticity and information processing in the brain.
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The characteristics and mechanisms of synchronized firing in developing networks of cultured cortical neurons were studied using multisite recording through planar electrode arrays (PEAs). With maturation of the network (from 3 to 40 d after plating), the frequency and propagation velocity of bursts increased markedly (approximately from 0.01 to 0.5 Hz and from 5 to 100 mm/sec, respectively), and the sensitivity to extracellular magnesium concentration (0-10 mM) decreased. The source of spontaneous bursts, estimated from the relative delay of onset of activity between electrodes, varied randomly with each burst. Physical separation of synchronously bursting networks into several parts using an ultraviolet laser, divided synchronous bursting into different frequencies and phases in each part. Focal stimulation through the PEA was effective at multiple sites in eliciting bursts, which propagated over the network from the site of stimulation. Stimulated bursts exhibited both an absolute refractory period and a relative refractory period, in which partially propagating bursts could be elicited. Periodic electrical stimulation (at 1 to 30 sec intervals) produced slower propagation velocities and smaller numbers of spikes per burst at shorter stimulation intervals. These results suggest that the generation and propagation of spontaneous synchronous bursts in cultured cortical neurons is governed by the level of spontaneous presynaptic firing, by the degree of connectivity of the network, and by a distributed balance between excitation and recovery processes.
1186/1471-2202-13-S1-P145 Cite this article as: Jarvs et al.: Axonal anisotropy and connectivity inhomogeneities in 2D networks
  • Doi
doi:10.1186/1471-2202-13-S1-P145 Cite this article as: Jarvs et al.: Axonal anisotropy and connectivity inhomogeneities in 2D networks. BMC Neuroscience 2012 13(Suppl 1): P145
Variability vs synchronicity of neuronal activity in local cortical network models with different wiring topologoes
  • K Kitano
  • T Fukai
Kitano K, Fukai T: Variability vs synchronicity of neuronal activity in local cortical network models with different wiring topologoes. J Comput Neurosci 2007, 23:237-250. doi:10.1186/1471-2202-13-S1-P145
Axonal anisotropy and connectivity inhomogeneities in 2D networks
  • Jarvs
Cite this article as: Jarvs et al.: Axonal anisotropy and connectivity inhomogeneities in 2D networks. BMC Neuroscience 2012 13(Suppl 1): P145.