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Inhomogeneities in network structure govern spontaneous activity

May 31, 2019: Networks of biological neurons can be spontaneously active. In absence of sensory input, neurons send and receive action potentials generated by the network itself. The connectivity between neurons is a key factor regulating the generation and propagation of such spontaneous activity but the exact mechanisms are not known and difficult to access in vivo. Researchers from the Bernstein Center Freiburg investigated the origin of spontaneous activity generation in networks of cultured cortical neurons. They found that spontaneous activity mainly originates in regions where such networks are inhomogeneous. Their findings have now been published in Frontiers in Neuroscience.

Inhomogeneities in network structure govern spontaneous activity

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For their research the neuroscientists have used large-scale micro-electrode arrays with about 1000 electrodes placed on one square centimeter. “These allow us to monitor activity from nearly the full extent of networks of 150,000 neurons”, explains Dr. Samora Okujeni from the Biomicrotechnology lab of Prof. Dr. Ulrich Egert. This gave new insights into the dynamics underlying the generation of spontaneous activity in large but confined networks that were sampled only across a much smaller region so far. To assess how connectivity influenced activity generation, networks were grown with homogenous and clustered cell body arrangements.

Inhomogeneities promote recurrent connectivity

As in many developing neuronal systems, cultured networks display bursts of activity that start spontaneously at distinct locations and then propagate into the network. In their networks, the scientists observed that initiation sites were widely distributed when neurons were distributed inhomogeneously but lay almost exclusively at the network boundary of homogenous networks. The research team suggests that clustering of neurons or asymmetric opportunities for connections in such regions promote recurrent connectivity and amplification of activity. In contrast, within a homogeneous region activity dissipates presumably because of a prevalence of divergent connectivity motifs. Samora Okujeni states: “This makes it more difficult to “heat up” the network sufficiently to initiate a network burst”. The researchers speculate that inhomogeneity is a key factor regulating spontaneous activity in the network.

Inhomogeneities govern spontaneous activity

Surprisingly, bursts were not initiated in network areas that display particularly high average levels of activity but rather at transitions between “hot” and “cold” zones with intermediate activity levels. “We suspect that these areas are not excessively firing within bursts and thus recover earlier to re-start the next burst. Identifying such basic relations between structure and function deepens the understanding of healthy and pathological dynamics and may point the path for future treatments. The role of the regions close to the boundary in activity generation, for instance, may explain why epileptic foci following brain insults in mice often appear in the transition zone between lesion and healthy tissue and not within the lesion zone itself.”, concludes Samora Okujeni.

Figure Caption
In cultured networks of 150,000 cortical neurons spontaneous activity is initiated locally and then propagates as a traveling wave until most neurons are recruited (from red to blue). Right top: In homogeneous networks, prominent initiation sites (1-9) are located close to the network boundary, whereas in clustered networks they also appear in more central areas (right bottom). Moreover, initiation sites are mostly situated in transition zones between highly (red) and weakly (blue) active network areas.

Networking
We sincerely thank Multichannel-Systems for providing us with the 1024-MEA system.

Original Publication
Okujeni S and Egert U (2019) Inhomogeneities in Network Structure and Excitability Govern Initiation and Propagation of Spontaneous Burst Activity. Front. Neurosci. 13:543. doi.org/10.3389/fnins.2019.00543

Contact
Dr. Samora Okujeni
Tel.: +49 (0)761 203 7523
E-mail: okujeni@bcf.uni-freiburg.de

Prof. Dr. Ulrich Egert
Tel.: +49 (0)761 203-7524
E-mail: egert@imtek.uni-freiburg.de

University of Freiburg
Bernstein Center Freiburg
Hansastr. 9a
79104 Freiburg
and
Faculty of Engineering
Biomicrotechnology, Dept. of Microsystems Engineering
Georges-Köhler-Allee 102
79110 Freiburg
 

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