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.
Highlights
The role of transcription factors during astrocyte development and their subsequent effects on neuronal development has been well studied
To screen for prospective regulators of adult astrocyte functions, we performed unbiased clustering based on unsupervised principal-component analysis and visualization using t-distributed stochastic neighbor embedding (t-SNE) and identified 4 distinct astrocyte clusters from a total of 36 populations (Fig. 1a, S1a)
Immunohistochemical staining in Aldh1L1-EGFP BAC transgenic mice, an established mouse line that labels astrocytes with EGFP37, showed that expression of Sox[9] in adult animals colocalized exclusively with EGFP in the olfactory bulb (OB), indicating that its expression is restricted to astrocytes (Fig. 1c)
Summary
The role of transcription factors during astrocyte development and their subsequent effects on neuronal development has been well studied. We examined the role of Sox[9] in adult OB astrocytes, finding that its deletion drastically altered astrocycte morphology and calcium handling activity These in vivo manipulations of astrocytes affected olfactory behaviors in mice, influencing both odor detection thresholds and odor discrimination. These observed alterations were accompanied by changes to neuronal sensory response maps, electrophysiological properties of M/T cells, and increased OSN innervation. Knockdown of GLT-1 in the OB via shRNAi generated phenotypes similar to those observed in Sox[9] KO animals, including altered astrocycte morphology and decreased odor discrimination Together, these studies illustrate the critical contributions of astrocytes to olfactory information processing, and further define a role for Sox[9] in adult astrocytes of the OB
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
