An increase of inhibition drives the developmental decorrelation of neural activity

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Abstract

Throughout development, the brain transits from early highly synchronous activity patterns to a mature state with sparse and decorrelated neural activity, yet the mechanisms underlying this process are poorly understood. The developmental transition has important functional consequences, as the latter state is thought to allow for more efficient storage, retrieval and processing of information. Here, we show that, in the mouse medial prefrontal cortex (mPFC), neural activity during the first two postnatal weeks decorrelates following specific spatial patterns. This process is accompanied by a concomitant tilting of excitation-inhibition (E-I) ratio towards inhibition. Using optogenetic manipulations and neural network modeling, we show that the two phenomena are mechanistically linked, and that a relative increase of inhibition drives the decorrelation of neural activity. Accordingly, in mice mimicking the etiology of neurodevelopmental disorders, subtle alterations in E-I ratio are associated with specific impairments in the correlational structure of spike trains. Finally, capitalizing on EEG data from newborn babies, we show that an analogous developmental transition takes place also in the human brain. Thus, changes in E-I ratio control the (de)correlation of neural activity and, by these means, its developmental imbalance might contribute to the pathogenesis of neurodevelopmental disorders.

Data availability

LFP and SUA data that were newly generated for this study are available at the following open-access repository: https://gin.g-node.org/mchini/development_EI_decorrelation.Code supporting the findings of this study is available at the following open-access repository: https://github.com/mchini/Chini_et_al_EI_decorrelation.

Article and author information

Author details

Mattia Chini

Institute of Developmental Neurophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

For correspondence
mattia.chini@zmnh.uni-hamburg.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5782-9720
Thomas Pfeffer

Center for Brain and Cognition, Universitat Pompeu Fabra, Barcelona, Spain

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9561-3085
Ileana Hanganu-Opatz

Institute of Developmental Neurophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Competing interests
The authors declare that no competing interests exist.

Funding

European Research Council (ERC-2015-CoG 681577)

Ileana Hanganu-Opatz

Marie Curie Training Network euSNN (MSCA-ITN-H2020-860563)

Ileana Hanganu-Opatz

Horizon 2020 Framework Programme (DEEPER 101016787)

Ileana Hanganu-Opatz

Deutsche Forschungsgemeinschaft (437610067,178316478 and 302153259)

Ileana Hanganu-Opatz

Landesforschungsfoerderung Hamburg (LFF76,LFF73)

Ileana Hanganu-Opatz

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were performed in compliance with the German laws and following the European Community guidelines regarding the research animals use. All experiments were approved by the local ethical committee (G132/12, G17/015, N18/015).

Human subjects: No new human data was collected for this study, only open-access datasets were used.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.