Network inhomogeneity supports burst initiation in vitro

Abstract

The emergence of spontaneous bursting events in developing neuronal networks likely depends on the evolving network connectivity. Theoretical models have shown that hierarchical network structures embedding clusters of strongly inter-connected neurons are optimal for initiating and sustaining spontaneous activity [1]. It is conceivable that activity-dependent wiring could innately support the formation of similar network structures.

To test this we chronically manipulated activity-dependent structural plasticity by inhibition of protein kinase C (PKC) in developing networks of cortical neurons in vitro. Previous studies showed that PKC inhibition in developing cerebellum promotes dendritic outgrowth and arborization of Purkinje cells and impairs pruning of climbing fibers. We found 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 (fig. 1A-B). As a result, propagation of activity within bursts was faster and occurred in strongly isotropic waves (fig. 1C-D). Interestingly, bursts in these networks were triggered from fewer sites and at much lower rates suggesting that the homogeneous networks forming under blockade of activity-dependent wiring processes embed fewer burst initiation zones.

Figure 1

MAP2 staining of dendrites and somata: control networks (A) display characteristic features of an activity-dependent wiring process including fasciculation and ramification of dendrites within clusters. Developmental inhibition of PKC (B) generates more ...

Full text

POSTER PRESENTATION Open Access
Network inhomogeneity supports burst initiation
in vitro
Samora Okujeni
1,2,3*
, Nila Moenig
2
, Steffen Kandler
1,2,3
, Oliver Weihberger
1,2,3
, Ulrich Egert
1,3
From Twentieth Annual Computational Neuroscience Meeting: CNS*2011
Stockholm, Sweden. 23-28 July 2011
The eme rgen ce of spontaneous bursting ev ents in devel-
oping neuronal networks likely depends on the evolving
network connectivity. Theoretical models have shown
that hierarchical network structures embedding clusters
of strongly inter-connected neurons are optimal for
initiating and sustaining spontaneous activity [1]. It is
conceivable th at activity-dependent wiring could innately
support the formation of similar network structures.
To test this we chr onically manipulated activity-
dependent structural plasticity by inhibition of protein
* Correspondence: okujeni@bcf.uni-freiburg.de
1
Bernstein Center Freiburg, Univ. Freiburg, Freiburg, Germany
Full list of author information is available at the end of the article
Figure 1 MAP2 staining of dendrites and somat a: control networks (A) display characteristic features of an activity-depen dent wiri ng process
including fasciculation and ramification of dendrites within clusters. Developmental inhibition of PKC (B) generates more homogeneous
networks in which neurites grow out ignoring neuronal neighbors. Propagation of activity in spontaneous and stimulation-induced bursts was
analyzed in micro-electrode recordings (first spike rank order from light to dark gray; black: no activity; white circles indicate stimulation sites):
bursts in control networks (C) display irregularities in the spatial propagation pattern indicating complex underlying structure. Homogeneous
networks developing under impaired PKC activity (D) show highly isotropic propagation patterns. Spontaneous (E) and elicited (F) propagation
patterns in controls are hardly comparable. Stimulation of homogeneous networks elicits highly isotropic propagation patterns (H) similar to
those in spontaneous bursts (G). Scale bars: 2mm.
Okujeni et al. BMC Neuroscience 2011, 12(Suppl 1):P84
http://www.biomedcentral.com/1471-2202/12/S1/P84
© 2011 Okujeni et a l; licensee BioM ed Central Ltd. This is an open ac cess article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/ licenses/by/2.0), which permits unrestricted u se, distribution, and reprod uction in
any me dium, provided the original work is properly cited.

kinase C (PKC) in developing networks of cortical neu-
rons in vitro. Previous studies showed that PKC inhibi-
tion in developing cerebellum promotes dendritic
outgrowth and arborization of Purkinje cells and impairs
pruning of climbing fibers. We found that developmen-
tal 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 (fig. 1A-B). As a result, propagation of activity
within bursts was faster and occurred in strongly isotro-
pic waves (fig. 1C-D). Interestingly, bursts in t hese net-
works were triggered from fewer sites a nd at much
lower rates suggesting that the homogeneous networks
forming under blockade of activity-dependent wiring
processes embed fewer burst initiation zones.
Acknowledgements
Funded by the German BMBF (FKZ 01GQ0420 & FKZ 01GQ0830) and by the
EC (NEURO, No. 12788)
Author details
1
Bernstein Center Freiburg, Univ. Freiburg, Freiburg, Germany.
2
Fac. Biol.,
Univ. Freiburg, Germany.
3
Fac. Engineer. – IMTEK, Univ. Freiburg, Germany.
Published: 18 July 2011
Reference
1. Kaiser M, Hilgetag CC: Optimal hierarchical modular topologies for
producing limited sustained activation of neural networks. Front Neuroinf
2010, 4(8):8.
doi:10.1186/1471-2202-12-S1-P84
Cite this article as: Okujeni et al.: Network inhomogeneity supports
burst initiation in vitro. BMC Neuroscience 2011 12(Suppl 1):P84.
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Okujeni et al. BMC Neuroscience 2011, 12(Suppl 1):P84
http://www.biomedcentral.com/1471-2202/12/S1/P84
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