Olfactory bulb astrocytes mediate sensory circuit processing through Sox9 in the mouse brain

Kevin Ung, Teng-Wei Huang, Brittney Lozzi, Junsung Woo, Elizabeth Hanson, Brandon Pekarek, Burak Tepe, Debosmita Sardar, Yi-Ting Cheng, Gary Liu, Benjamin Deneen () and Benjamin R. Arenkiel ()
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Kevin Ung: Baylor College of Medicine
Teng-Wei Huang: Baylor College of Medicine
Brittney Lozzi: Baylor College of Medicine
Junsung Woo: Baylor College of Medicine
Elizabeth Hanson: Baylor College of Medicine
Brandon Pekarek: Baylor College of Medicine
Burak Tepe: Baylor College of Medicine
Debosmita Sardar: Baylor College of Medicine
Yi-Ting Cheng: Baylor College of Medicine
Gary Liu: Baylor College of Medicine
Benjamin Deneen: Baylor College of Medicine
Benjamin R. Arenkiel: Baylor College of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract The role of transcription factors during astrocyte development and their subsequent effects on neuronal development has been well studied. Less is known about astrocytes contributions towards circuits and behavior in the adult brain. Astrocytes play important roles in synaptic development and modulation, however their contributions towards neuronal sensory function and maintenance of neuronal circuit architecture remain unclear. Here, we show that loss of the transcription factor Sox9 results in both anatomical and functional changes in adult mouse olfactory bulb (OB) astrocytes, affecting sensory processing. Indeed, astrocyte-specific deletion of Sox9 in the OB results in decreased odor detection thresholds and discrimination and it is associated with aberrant neuronal sensory response maps. At functional level, loss of astrocytic Sox9 impairs the electrophysiological properties of mitral and tufted neurons. RNA-sequencing analysis reveals widespread changes in the gene expression profiles of OB astrocytes. In particular, we observe reduced GLT-1 expression and consequential alterations in glutamate transport. Our findings reveal that astrocytes are required for physiological sensory processing and we identify astrocytic Sox9 as an essential transcriptional regulator of mature astrocyte function in the mouse OB.

Date: 2021
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DOI: 10.1038/s41467-021-25444-3

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