Activity-dependent modulation of synapse-regulating genes in astrocytes

eLife

Hanqing Liu¹  Joseph R Ecker²  Cari Dowling³  Nicola J Allen³  Matthew M Boisvert³  Isabella Farhy-Tselnicker³  Elena Blanco-Suarez³  Galina A Erikson⁴  Maxim N Shokhirev⁴  Chen Farhy⁵ 

[1] Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, United States;Division of Biological Sciences, University of California San Diego, La Jolla, United States;Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, United States;Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, United States;Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, United States;Razavi Newman Integrative Genomics and Bioinformatics Core, The Salk Institute for Biological Studies, La Jolla, United States;Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States;

关键词: astrocytes;    synaptic terminals;    visual development;    gene expression;    neuronal activity;    Mouse;   

DOI  :  10.7554/eLife.70514

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 is 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.

【 授权许可】

CC BY