Bajar Bryce T, Phi Nguyen T, Randhawa Harpreet, Akin Orkun
Department of Biological Chemistry, Medical Scientist Training Program, Neuroscience Interdepartmental Program, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Dev Neurobiol. 2022 Apr;82(3):235-244. doi: 10.1002/dneu.22870. Epub 2022 Mar 11.
Developmental neural activity is a common feature of neural circuit assembly. Although glia have established roles in synapse development, the contribution of neuron-glia interactions to developmental activity remains largely unexplored. Here we show that astrocytes are necessary for developmental activity during synaptogenesis in Drosophila. Using wide-field epifluorescence and two-photon imaging, we show that the glia of the central nervous system participate in developmental activity with type-specific patterns of intracellular calcium dynamics. Genetic ablation of astrocytes, but not of cortex or ensheathing glia, leads to severe attenuation of neuronal activity. Similarly, inhibition of neuronal activity results in the loss of astrocyte calcium dynamics. By altering these dynamics, we show that astrocytic calcium cycles can influence neuronal activity but are not necessary per se. Taken together, our results indicate that, in addition to their recognized role in the structural maturation of synapses, astrocytes are also necessary for the function of synapses during development.
发育中的神经活动是神经回路组装的一个共同特征。尽管神经胶质细胞在突触发育中已确立了作用,但神经元与神经胶质细胞的相互作用对发育活动的贡献在很大程度上仍未得到探索。在这里,我们表明星形胶质细胞对于果蝇突触发生过程中的发育活动是必不可少的。利用宽场落射荧光和双光子成像,我们表明中枢神经系统的神经胶质细胞以细胞内钙动力学的类型特异性模式参与发育活动。星形胶质细胞的基因消融,而非皮质或包被神经胶质细胞的消融,会导致神经元活动严重减弱。同样,抑制神经元活动会导致星形胶质细胞钙动力学丧失。通过改变这些动力学,我们表明星形胶质细胞的钙循环可以影响神经元活动,但本身并非必需。综上所述,我们的结果表明,除了在突触结构成熟中公认的作用外,星形胶质细胞对于发育过程中突触的功能也是必不可少的。