Investigating the interplay between segregation and integration in developing cortical assemblies

Valerio Barabino; Ilaria Donati Della Lunga; Francesca Callegari; Letizia Cerutti; Fabio Poggio; Mariateresa Tedesco; Paolo Massobrio; Martina Brofiga

doi:10.3389/fncel.2024.1429329

Investigating the interplay between segregation and integration in developing cortical assemblies

Front Cell Neurosci. 2024 Sep 12:18:1429329. doi: 10.3389/fncel.2024.1429329. eCollection 2024.

Authors

Valerio Barabino^#¹, Ilaria Donati Della Lunga^#¹, Francesca Callegari¹, Letizia Cerutti^{1

2}, Fabio Poggio¹, Mariateresa Tedesco¹, Paolo Massobrio^{1

3}, Martina Brofiga^{1

2

4}

Affiliations

¹ Department of Informatics, Bioengineering, Robotics and Systems Engineering (DIBRIS), University of Genova, Genova, Italy.
² Neurofacility, Istituto Italiano di Tecnologia, Genova, Italy.
³ National Institute for Nuclear Physics (INFN), Genova, Italy.
⁴ ScreenNeuroPharm S.r.l, Sanremo, Italy.

^# Contributed equally.

Abstract

Introduction: The human brain is an intricate structure composed of interconnected modular networks, whose organization is known to balance the principles of segregation and integration, enabling rapid information exchange and the generation of coherent brain states. Segregation involves the specialization of brain regions for specific tasks, while integration facilitates communication among these regions, allowing for efficient information flow. Several factors influence this balance, including maturation, aging, and the insurgence of neurological disorders like epilepsy, stroke, or cancer. To gain insights into information processing and connectivity recovery, we devised a controllable in vitro model to mimic and investigate the effects of different segregation and integration ratios over time.

Methods: We designed a cross-shaped polymeric mask to initially establish four independent sub-populations of cortical neurons and analyzed how the timing of its removal affected network development. We evaluated the morphological and functional features of the networks from 11 to 18 days in vitro (DIVs) with immunofluorescence techniques and micro-electrode arrays (MEAs).

Results: The removal of the mask at different developmental stages of the network lead to strong variations in the degree of intercommunication among the four assemblies (altering the segregation/integration balance), impacting firing and bursting parameters. Early removal (after 5 DIVs) resulted in networks with a level of integration similar to homogeneous controls (without physical constraints). In contrast, late removal (after 15 DIVs) hindered the formation of strong inter-compartment connectivity, leading to more clustered and segregated assemblies.

Discussion: A critical balance between segregation and integration was observed when the mask was removed at DIV 10, allowing for the formation of a strong connectivity among the still-separated compartments, thus demonstrating the existence of a time window in network development in which it is possible to achieve a balance between segregation and integration.

Keywords: PDMS device; connectivity; cortical networks; integration; micro-electrode arrays; segregation.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by #NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006)—a multiscale integrated approach to the study of nervous system in health and disease (DN. 1553 11.10.2022).