Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
J Neurosci Res. 2020 Aug;98(8):1605-1618. doi: 10.1002/jnr.24634. Epub 2020 May 19.
Astrocytes are the most abundant glial cell in the central nervous system. They modulate synaptic function through a variety of mechanisms, and yet remain relatively understudied with respect to overall neuronal circuit function. Exploiting the tractability of the mouse olfactory system, we manipulated astrocyte activity and examined how astrocytes modulate olfactory bulb responses. Toward this, we genetically targeted both astrocytes and neurons for in vivo widefield imaging of Ca responses to odor stimuli. We found that astrocytes exhibited odor response maps that overlap with excitatory neuronal activity. By manipulating Ca activity in astrocytes using chemical genetics we found that odor-evoked neuronal activity was reciprocally affected, suggesting that astrocyte activation inhibits neuronal odor responses. Subsequently, behavioral experiments revealed that astrocyte manipulations affect both odor detection threshold and discrimination, suggesting that astrocytes play an active role in olfactory sensory processing circuits. Together, these studies show that astrocyte calcium signaling contributes to olfactory behavior through modulation of sensory circuits.
星形胶质细胞是中枢神经系统中最丰富的神经胶质细胞。它们通过多种机制调节突触功能，但相对于整体神经元回路功能的研究仍相对较少。利用小鼠嗅觉系统的可操作性，我们操纵星形胶质细胞的活性，并研究星形胶质细胞如何调节嗅球反应。为此，我们对星形胶质细胞和神经元进行了基因靶向，以进行体内宽场成像，从而对气味刺激的 Ca 反应进行成像。我们发现星形胶质细胞表现出与兴奋性神经元活动重叠的气味反应图。通过使用化学生物学操纵星形胶质细胞中的 Ca 活性，我们发现气味诱发的神经元活动会相互影响，这表明星形胶质细胞的激活抑制了神经元对气味的反应。随后，行为实验表明星形胶质细胞的操作会影响气味检测阈值和辨别能力，这表明星形胶质细胞在嗅觉感觉处理回路中发挥着积极的作用。总之，这些研究表明，星形胶质细胞钙信号通过调节感觉回路对嗅觉行为有贡献。
