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

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.

Cranial and Spinal Window Preparation for in vivo Optical Neuroimaging in Rodents and Related Experimental Techniques

“…Of cautioning note, the insertion of electrodes would induce unavoidable damage to the tissue, and the imaging FOV would also be restricted by the electrode. Single electrode insertion to the exposed brain could be sufficient in some cases; [63,67,89] however, specialized design and devices (e.g., micro electric mechanical system: MEMS) and/or implementation of multi-channel recording setup may be necessary for effective assessment of the 3D neural structures [39,42,108,117]. When performing imaging using a cranial and spinal window with a behaving animal, spatial arrangements of the microscope stage are crucial considering FOV, the working distance of the objective lens, anesthesia setting, and proper monitoring of the animal under experiment.…”

“…While the cranial and spinal window enables efficient 2D wide-field imaging, information collected from optical neuroimaging often suffers from the constraint of superficial information. For studies of 3D functional neurodynamics, simultaneous acquisition of neuroelectric signals using electrophysiology in the targeted brain areas at variable depths can be adopted [ 39 , 42 , 63 , 108 , 117 ].…”

“…Of cautioning note, the insertion of electrodes would induce unavoidable damage to the tissue, and the imaging FOV would also be restricted by the electrode. Single electrode insertion to the exposed brain could be sufficient in some cases; [ 63 , 67 , 89 ] however, specialized design and devices (e.g., micro electric mechanical system: MEMS) and/or implementation of multi-channel recording setup may be necessary for effective assessment of the 3D neural structures [ 39 , 42 , 108 , 117 ].…”

“…The type of cranial and spinal window can be decided based on the region of interest (ROI) to be examined with the microscope. Here we describe various types of cranial windows such as the olfactory bulb [ 18 , 60 - 64 ], somatosensory cortex [ 34 , 35 , 65 , 66 ], visual cortex [ 31 , 44 , 67 ], hippocampus [ 68 - 70 ], cerebellum [ 71 , 72 ], medial entorhinal cortex [ 73 ], and the spinal cord chamber window (SCCW) [ 21 - 23 ]. Fig.…”

Astrocyte and Oligodendrocyte Responses From the Subventricular Zone After Injury

“…The transcription factor Sox9 regulates induction of NFIA and plays a crucial role in the onset of gliogenesis (Stolt et al, 2003;Kang et al, 2012), while activation of Notch1 during neuroectodermal differentiation has been shown to upregulate Sox9 expression (Martini et al, 2013). Furthermore, in adult astrocytes, Sox9-expression is required to maintain morphological integrity of astrocytes in the olfactory bulb (Ung et al, 2021). Overexpression of Sox9 in the adult SVZ suppresses production of neurons from NSCs, whereas Sox9 knockdown stimulates neurogenesis and inhibits gliogenesis (Cheng et al, 2009) indicating that Sox9 promotes astrogenesis in SVZ-NSC populations.…”