A transient postnatal quiescent period precedes emergence of mature cortical dynamics
- Columbia University, United States
- Harvard University, United States
- Max Planck, Germany
- New York University, United States
- Harvard Medical School, United States
Abstract
Mature neural networks synchronize and integrate spatiotemporal activity patterns to support cognition. Emergence of these activity patterns and functions is believed to be developmentally regulated, but the postnatal time course for neural networks to perform complex computations remains unknown. We investigate the progression of large-scale synaptic and cellular activity patterns across development using high spatiotemporal resolution in vivo electrophysiology in immature mice. We reveal that mature cortical processes emerge rapidly and simultaneously after a discrete but volatile transition period at the beginning of the second postnatal week of rodent development. The transition is characterized by relative neural quiescence, after which spatially distributed, temporally precise, and internally organized activity occurs. We demonstrate a similar developmental trajectory in humans, suggesting an evolutionarily conserved mechanism that could facilitate a transition in network operation. We hypothesize that this transient quiescent period is a requisite for the subsequent emergence of coordinated cortical networks.
Data availability
Source data are presented in Supplementary Figures and uploaded to Dryad. Data pertaining to human subjects is governed by IRB policy and can be accessed through application to the IRB. Pooled, processed human subject data are uploaded to Dryad.
-
A transient postnatal quiescent period precedes emergence of mature cortical dynamicsDryad Digital Repository, doi:10.5061/dryad.15dv41nxp.
Article and author information
Author details
Jennifer N Gelinas
Funding
National Institutes of Health (R21 EY032381)
- Dion Khodagholy
- Jennifer N Gelinas
H2020 European Research Council (Marie Skłodowska-Curie grant agreement No 799501)
- Soledad Dominguez
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sacha B Nelson, Brandeis University, United States
Ethics
Animal experimentation: All animal experiments were performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and approved by the Institutional Animal Care and Use Committee at Columbia University Irving Medical Center.protocol AABI5568.
Human subjects: We retrospectively analyzed EEG recordings from 54 patients who underwent continuous monitoring with surface electroencephalography (EEG) as part of clinical diagnostic assessment. Analysis of these data were approved by the Institutional Review Board at Columbia University Irving Medical Center, and all data collection occurred at this institution. All data reviewed was initially obtained for clinical management purposes and informed consent was waived as per 45 CFR 46.116.
Version history
- Preprint posted: February 17, 2021 (view preprint)
- Received: April 1, 2021
- Accepted: June 26, 2021
- Accepted Manuscript published: July 23, 2021 (version 1)
- Version of Record published: August 11, 2021 (version 2)
Copyright
© 2021, Dominguez et al.
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.
Metrics
-
- 1,792
- views
-
- 311
- downloads
-
- 11
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
A transient postnatal quiescent period precedes emergence of mature cortical dynamics
eLife 10:e69011.
https://doi.org/10.7554/eLife.69011
Further reading
-
- Neuroscience
Negative memories engage a brain and body-wide stress response in humans that can alter cognition and behavior. Prolonged stress responses induce maladaptive cellular, circuit, and systems-level changes that can lead to pathological brain states and corresponding disorders in which mood and memory are affected. However, it is unclear if repeated activation of cells processing negative memories induces similar phenotypes in mice. In this study, we used an activity-dependent tagging method to access neuronal ensembles and assess their molecular characteristics. Sequencing memory engrams in mice revealed that positive (male-to-female exposure) and negative (foot shock) cells upregulated genes linked to anti- and pro-inflammatory responses, respectively. To investigate the impact of persistent activation of negative engrams, we chemogenetically activated them in the ventral hippocampus over 3 months and conducted anxiety and memory-related tests. Negative engram activation increased anxiety behaviors in both 6- and 14-month-old mice, reduced spatial working memory in older mice, impaired fear extinction in younger mice, and heightened fear generalization in both age groups. Immunohistochemistry revealed changes in microglial and astrocytic structure and number in the hippocampus. In summary, repeated activation of negative memories induces lasting cellular and behavioral abnormalities in mice, offering insights into the negative effects of chronic negative thinking-like behaviors on human health.
-
- Neuroscience
Synaptic inputs to cortical neurons are highly structured in adult sensory systems, such that neighboring synapses along dendrites are activated by similar stimuli. This organization of synaptic inputs, called synaptic clustering, is required for high-fidelity signal processing, and clustered synapses can already be observed before eye opening. However, how clustered inputs emerge during development is unknown. Here, we employed concurrent in vivo whole-cell patch-clamp and dendritic calcium imaging to map spontaneous synaptic inputs to dendrites of layer 2/3 neurons in the mouse primary visual cortex during the second postnatal week until eye opening. We found that the number of functional synapses and the frequency of transmission events increase several fold during this developmental period. At the beginning of the second postnatal week, synapses assemble specifically in confined dendritic segments, whereas other segments are devoid of synapses. By the end of the second postnatal week, just before eye opening, dendrites are almost entirely covered by domains of co-active synapses. Finally, co-activity with their neighbor synapses correlates with synaptic stabilization and potentiation. Thus, clustered synapses form in distinct functional domains presumably to equip dendrites with computational modules for high-capacity sensory processing when the eyes open.
