Publication Date
6-16-2023
Journal
Science
DOI
10.1126/science.ade0027
PMID
37319217
PMCID
PMC10874521
PubMedCentral® Posted Date
2-18-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Animals, Mice, Astrocytes, gamma-Aminobutyric Acid, Histones, Synaptic Transmission, Organic Cation Transport Proteins, Serotonin, Olfactory Bulb, Epigenesis, Genetic, Olfactory Perception
Abstract
Neuronal activity drives alterations in gene expression within neurons, yet how it directs transcriptional and epigenomic changes in neighboring astrocytes in functioning circuits is unknown. We found that neuronal activity induces widespread transcriptional upregulation and downregulation in astrocytes, highlighted by the identification of a neuromodulator transporter Slc22a3 as an activity-inducible astrocyte gene regulating sensory processing in the olfactory bulb. Loss of astrocytic Slc22a3 reduced serotonin (5HT) levels in astrocytes, leading to alterations in histone serotonylation. Inhibition of histone serotonylation in astrocytes reduced expression of GABA biosynthetic genes and GABA release, culminating in olfactory deficits. Our study revealed that neuronal activity orchestrates transcriptional and epigenomic responses in astrocytes, while illustrating new mechanisms for how astrocytes process neuromodulatory input to gate neurotransmitter release for sensory processing.