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Impaired structural plasticity increases connectivity in developing cortical networks

Authors:
Samora Okujeni at University of Freiburg
Samora Okujeni
Steffen Kandler
Steffen Kandler
Steffen Kandler
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Oliver Weihberger at inomed Medizintechnik GmbH
Oliver Weihberger
  • inomed Medizintechnik GmbH
Ulrich Egert at University of Freiburg
Ulrich Egert
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BioMed Central
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BMC Neuroscience
Open Access
Poster presentation
Impaired structural plasticity increases connectivity in developing
cortical networks
Samora Okujeni*1,2, Steffen Kandler1,2, Oliver Weihberger1,2 and
Ulrich Egert1,3
Address: 1Bernstein Center for Computational Neuroscience, University Freiburg, Germany, 2Institute of Biology III, Neurobiology and Biophysics,
University Freiburg, Germany and 3Biomicrotechnology, Department of Microsystems Engineering, University Freiburg, Germany
Email: Samora Okujeni* - okujeni@bccn.uni-freiburg.de
* Corresponding author
The principle of self-organization is fundamental for the
adaptive formation and modification of functional cir-
cuits in many parts of the nervous system. At a cellular
level, cortical micro-circuitry evolves on the basis of activ-
ity-dependent biochemical processes that guide neuronal
wiring and that are differentially regulated in the course of
development. Protein kinase C (PKC) plays a key-role in
this morphological differentiation of neurons, since it
cross-links many biochemical pathways involved in struc-
tural regulation and targets many cytoskeletal proteins
directly. In a simplified model, activation of PKC via
metabotropic glutamate receptor downstream signaling
phosphorylates and mobilizes cytoskeletal proteins and
thereby promotes structural plasticity [1]. Antagonistic
pathways that involve NMDA receptor mediated activa-
tion of protein phosphatases in turn promote cytoskeletal
assembly and stabilization.
We explore this concept of structural homeostasis in dis-
sociated cortical cell cultures developing on microelec-
trode arrays. These generic random networks display a
self-regulated maturation process with similar phases as
the developing cortex. Within this period of network for-
mation we interfered with the structural homeostasis by
inhibiting PKC activity. Previous studies showed that
inhibition of PKC activity in cerebellar slice cultures pro-
motes dendritic outgrowth and arborization in Purkinje
cells [2] and that climbing fiber pruning is impaired in
PKC deficient mice [3]. Further in vitro data demonstrate
the importance of PKC activity for the experience-depend-
ent modulation of synaptic weights on the basis of AMPA
receptor trafficking [4], suggesting reduced synaptic plas-
ticity under PKC inhibition.
To assess possible functional consequences of these
dependencies, we chronically inhibited PKC activity in
cortical cell cultures and compared network activity and
connectivity characteristics. Applying new morphomet-
rics, we found significantly increased arborization and
extent of dendrites as well as increased synapse density,
indicating increased connectivity in these networks. Fur-
ther, we observed reduced neuronal clustering suggesting
impaired cell migration. These findings indicate changes
in the connectivity statistics in networks developing under
inhibited PKC activity that fit to the assumed homeostatic
model of structural regulation. Irrespective of PKC inhibi-
tion, spike activity remained organized in network-wide
bursting that characteristically emerges in cortical cell cul-
tures. Bursts were, however, more synchronized across the
recording area and contained more spikes, suggesting a
faster propagation of activity through the networks and
longer reverberations due to increased connectivity. Dif-
ferences in the spatio-temporal spread of activity at differ-
ent stages of development further indicate a more
homogeneous topology under PKC inhibition. This could
be the result of a stronger conservation of the highly con-
from Eighteenth Annual Computational Neuroscience Meeting: CNS*2009
Berlin, Germany. 18–23 July 2009
Published: 13 July 2009
BMC Neuroscience 2009, 10(Suppl 1):P208 doi:10.1186/1471-2202-10-S1-P208
<supplement> <title> <p>Eighteenth Annual Computational Neuroscience Meeting: CNS*2009</p> </title> <editor>Don H Johnson</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1471-2202-10-S1-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2202-10-S1-info.pdf</url> </supplement>
This abstract is available from: http://www.biomedcentral.com/1471-2202/10/S1/P208
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nected and unclustered immature network structure. In
summary, consistence between our morphological and
electrophysiological data support the idea that coordi-
nated regulation of PKC activity is required for a proper
formation of functional pathways in early network devel-
opment.
Acknowledgements
Supported by the German Federal Ministry of Education and Research
(FKZ 01GQ0420) and the European Community (Neuro, No. 12788).
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... Behaviour of animals depends in the main on how brain cells are interconnected (Hohnke & Sur, 2002). Neuro-networks begin with morphological differentiation of neurons followed by increased arborisation, extension of dendrites and increased synaptic density yielding a network of reciprocally interacting units organised for a particular function or functions (Okujeni, Kandler, Weihberger, & Egert, 2009). These 'loops' of neurons are initially imprecise connections that with maturity become increasingly precise (Hohnke & Sur, 2002). ...
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