Activity-dependent modulation of synapse-regulating genes in astrocytes
- Salk Institute for Biological Studies, United States
- Thomas Jefferson University, United States
- Sanford Burnham Prebys Medical Discovery Institute, United States
- The Salk Institute for Biological Studies, United States
- Howard Hughes Medical Institute, Salk Institute for Biological Studies, United States
Abstract
Astrocytes regulate the formation and function of neuronal synapses via multiple signals, however, what controls regional and temporal expression of these signals during development is unknown. We determined the expression profile of astrocyte synapse-regulating genes in the developing mouse visual cortex, identifying astrocyte signals that show differential temporal and layer-enriched expression. These patterns are not intrinsic to astrocytes, but regulated by visually-evoked neuronal activity, as they are absent in mice lacking glutamate release from thalamocortical terminals. Consequently, synapses remain immature. Expression of synapse-regulating genes and synaptic development are also altered when astrocyte signaling is blunted by diminishing calcium release from astrocyte stores. Single nucleus RNA sequencing identified groups of astrocytic genes regulated by neuronal and astrocyte activity, and a cassette of genes that show layer-specific enrichment. Thus, the development of cortical circuits requires coordinated signaling between astrocytes and neurons, highlighting astrocytes as a target to manipulate in neurodevelopmental disorders.
Data availability
DATA AVAILABILITYAll data supporting the results of this study can be found in the following locations:Processed RNA sequencing data presented in Figure 1 is available in Figure 1- Source Data 1.Data presented in graphs in Figures 2-5 is available in Figure 2-5 Source Data files.Processed single nucleus RNA sequencing data presented in Figure 6 is available in Figure 6-Source Data 1.The RNA sequencing data has been deposited at GEO. Ribotag data is available at GSE161398 and glial snRNAseq at GSE163775.Processed RNA sequencing data is available in a searchable format at the following web locations:Ribotag astrocyte developmental dataset:igc1.salk.edu:3838/astrocyte_transcriptomeSingle nucleus glial cell sequencing:mouse-astro-dev.cells.ucsc.edu
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Astrocyte developmental transcriptome from mouse visual cortexNCBI Gene Expression Omnibus, GSE161398.
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Activity-dependent modulation of synapse-regulating genes in astrocytesNCBI Gene Expression Omnibus, GSE163775.
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Astrocyte-enriched pan-brain aging transcriptomeNCBI Gene Expression Omnibus, GSE99791.
Article and author information
Author details
Isabella Farhy-Tselnicker
Elena Blanco-Suarez
Funding
National Institutes of Health (NS105742)
- Nicola J Allen
National Institutes of Health (NS089791)
- Nicola J Allen
Pew Charitable Trusts
- Nicola J Allen
Chan Zuckerberg Initiative (2018-191894)
- Nicola J Allen
Howard Hughes Medical Institute
- Joseph R Ecker
National Institutes of Health (NIH NCI CCSG P30 014195)
- Maxim N Shokhirev
Hearst Foundations
- Nicola J Allen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal work was approved by the Salk Institute Institutional Animal Care and Use Committee (IACUC) protocol 12-00023.
Copyright
© 2021, Farhy-Tselnicker 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.
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Activity-dependent modulation of synapse-regulating genes in astrocytes
eLife 10:e70514.
https://doi.org/10.7554/eLife.70514
