Abstract
Damage in biological neuronal networks triggers a complex functional reorganization whose mechanisms are still poorly understood. To delineate this reorganization process, here we investigate the functional alterations of in vitro rat cortical circuits following localized laser ablation. The analysis of the functional network configuration before and after ablation allowed us to quantify the extent of functional alterations and the characteristic spatial and temporal scales along recovery. We observed that damage precipitated a fast rerouting of information flow that restored network’s communicability in about 15 min. Functional restoration was led by the immediate neighbors around trauma but was orchestrated by the entire network. Our in vitro setup exposes the ability of neuronal circuits to articulate fast responses to acute damage, and may serve as a proxy to devise recovery strategies in actual brain circuits. Moreover, this biological setup can become a benchmark to empirically test network theories about the spontaneous recovery in dynamical networks.
Significance Statement Given the sheer size of the brain, in vitro models in the form of neuronal cultures have emerged as a promising tool to investigate dynamic and network alterations in detail upon physical damage. Here we present a new experimental paradigm based on the combination of laser microsurgery and calcium fluorescence imaging to analyze network functional alterations after a focal lesion. We show that the network is not only able to cope with damage but that the regions around the lesion core actively participate in recovery, restoring the initial network activity levels in just 15 min. Our approach offers interesting perspectives for modeling network functional loss and recovery in a number of damage actions, from stroke to degenerative disorders.
- Calcium imaging
- Focal Damage
- Functional recovery
- Laser microsurgery
- Network Neuroscience
- Neuronal Cultures
Footnotes
Authors report no conflict of interest.
This research is part of MESO-BRAIN. The MESO-BRAIN Project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement no. 713140 (ST, EE, JA, OO, PL, JS). JS and ST acknowledge financial support from the Spanish Ministerio de Economia y Competitividad through projects no. FIS2013-41144-P, FIS2016-78507-C2-2-P and FIS2017-90782-REDT (IBERSINC), and from the Generalitat de Catalunya through grant no. 2017-SGR-1061. CG acknowledges financial support from the James S. McDonnell Foundation Postdoctoral Fellowship, grant no. 220020457. AA acknowledges financial support from Generalitat de Catalunya project 2017-SGR-896, Spanish MINECO projects FIS2015-71582-C2-1 and FIS2017-90782-REDT, ICREA Academia and the James S. McDonnell Foundation, grant no. 220020325. JA, OO and PL acknowledge financial support from the Spanish Ministerio de Economia y Competitividad (AEI/FEDER) through project no. FIS2016-80455-R, the ‘Severo Ochoa’ Programme for Centers of Excellence in R&D (SEV-2015-0522), Fundació Privada Cellex, Fundación Mig-Puig, Generalitat de Catalunya through the CERCA program and Laserlab-Europe (EU-H2020 654148).
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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