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Growth Rules for the Repair of Asynchronous Irregular Neuronal Networks after Peripheral Lesions

View ORCID ProfileAnkur Sinha, Christoph Metzner, Neil Davey, Roderick Adams, Michael Schmuker, Volker Steuber
doi: https://doi.org/10.1101/810846
Ankur Sinha
1UH Biocomputation Research Group, Centre for Computer Science and Informatics Research, University of Hertfordshire, Hatfield UK
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  • ORCID record for Ankur Sinha
Christoph Metzner
1UH Biocomputation Research Group, Centre for Computer Science and Informatics Research, University of Hertfordshire, Hatfield UK
2Department of Software Engineering and Theoretical Computer Science, Technische Universität Berlin, Berlin, Germany
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Neil Davey
1UH Biocomputation Research Group, Centre for Computer Science and Informatics Research, University of Hertfordshire, Hatfield UK
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Roderick Adams
1UH Biocomputation Research Group, Centre for Computer Science and Informatics Research, University of Hertfordshire, Hatfield UK
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Michael Schmuker
1UH Biocomputation Research Group, Centre for Computer Science and Informatics Research, University of Hertfordshire, Hatfield UK
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Volker Steuber
1UH Biocomputation Research Group, Centre for Computer Science and Informatics Research, University of Hertfordshire, Hatfield UK
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Abstract

Several homeostatic mechanisms enable the brain to maintain desired levels of neuronal activity. One of these, homeostatic structural plasticity, has been reported to restore activity in networks disrupted by peripheral lesions by altering their neuronal connectivity. While multiple lesion experiments have studied the changes in neurite morphology that underlie modifications of synapses in these networks, the underlying mechanisms that drive these changes are yet to be explained. Evidence suggests that neuronal activity modulates neurite morphology and may stimulate neurites to selective sprout or retract to restore network activity levels. We developed a new spiking network model, simulations of which accurately reproduce network rewiring after peripheral lesions as reported in experiments, to study these activity dependent growth regimes of neurites. To ensure that our simulations closely resemble the behaviour of networks in the brain, we deafferent a biologically realistic network model that exhibits low frequency Asynchronous Irregular (AI) activity as observed in cerebral cortex.

Our simulation results indicate that the re-establishment of activity in neurons both within and outside the deprived region, the Lesion Projection Zone (LPZ), requires opposite activity dependent growth rules for excitatory and inhibitory post-synaptic elements. Analysis of these growth regimes indicates that they also contribute to the maintenance of activity levels in individual neurons. Furthermore, in our model, the directional formation of synapses that is observed in experiments requires that pre-synaptic excitatory and inhibitory elements also follow opposite growth rules. Lastly, we observe that our proposed model of homeostatic structural plasticity and the inhibitory synaptic plasticity mechanism that also balances our AI network are both necessary for successful rewiring of the network.

Author summary An accumulating body of evidence suggests that our brain can compensate for peripheral lesions by adaptive rewiring of its neuronal circuitry. The underlying process, structural plasticity, can modify the connectivity of neuronal networks in the brain, thus affecting their function. To better understand the mechanisms of structural plasticity in the brain, we have developed a novel model of peripheral lesions and the resulting activity-dependent rewiring in a simplified cortical network model that exhibits biologically realistic asynchronous irregular activity. In order to accurately reproduce the directionality and time course of rewiring after injury that is observed in peripheral lesion experiments, we derive activity dependent growth rules for different synaptic elements: dendritic and axonal contacts. Our simulation results suggest that excitatory and inhibitory synaptic elements have to react to changes in neuronal activity in opposite ways. We show that these rules result in a homeostatic stabilisation of activity in individual neurons. In our simulations, both synaptic and structural plasticity mechanisms are necessary for network repair. Furthermore, our simulations indicate that while activity is restored in neurons deprived by the peripheral lesion, the temporal firing characteristics of the network can be changed by the rewiring process.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* a.sinha2{at}herts.ac.uk

  • Figure 11 was added to improve the section on the "activity dependent dynamics of pre-synaptic structures".

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted April 21, 2020.
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Growth Rules for the Repair of Asynchronous Irregular Neuronal Networks after Peripheral Lesions
Ankur Sinha, Christoph Metzner, Neil Davey, Roderick Adams, Michael Schmuker, Volker Steuber
bioRxiv 810846; doi: https://doi.org/10.1101/810846
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Growth Rules for the Repair of Asynchronous Irregular Neuronal Networks after Peripheral Lesions
Ankur Sinha, Christoph Metzner, Neil Davey, Roderick Adams, Michael Schmuker, Volker Steuber
bioRxiv 810846; doi: https://doi.org/10.1101/810846

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