Department of Biological Chemistry, Medical Scientist Training Program, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, USA.
Molecular, Cellular, and Integrative Physiology Interdepartmental Graduate Program, University of California, Los Angeles, Los Angeles, CA, USA.
Nature. 2022 Feb;602(7898):639-646. doi: 10.1038/s41586-022-04406-9. Epub 2022 Feb 9.
In vertebrates, stimulus-independent activity accompanies neural circuit maturation throughout the developing brain. The recent discovery of similar activity in the developing Drosophila central nervous system suggests that developmental activity is fundamental to the assembly of complex brains. How such activity is coordinated across disparate brain regions to influence synaptic development at the level of defined cell types is not well understood. Here we show that neurons expressing the cation channel transient receptor potential gamma (Trpγ) relay and pattern developmental activity throughout the Drosophila brain. In trpγ mutants, activity is attenuated globally, and both patterns of activity and synapse structure are altered in a cell-type-specific manner. Less than 2% of the neurons in the brain express Trpγ. These neurons arborize throughout the brain, and silencing or activating them leads to loss or gain of brain-wide activity. Together, these results indicate that this small population of neurons coordinates brain-wide developmental activity. We propose that stereotyped patterns of developmental activity are driven by a discrete, genetically specified network to instruct neural circuit assembly at the level of individual cells and synapses. This work establishes the fly brain as an experimentally tractable system for studying how activity contributes to synapse and circuit formation.
在脊椎动物中,刺激独立性活动伴随着整个发育大脑中神经回路的成熟。最近在发育中的果蝇中枢神经系统中发现了类似的活动,这表明发育活动对于复杂大脑的组装是基本的。这种活动如何在不同的脑区之间协调,以影响特定细胞类型的突触发育,目前还不是很清楚。在这里,我们表明表达阳离子通道瞬时受体潜力γ(Trpγ)的神经元在果蝇大脑中传递和塑造发育活动。在 trpγ 突变体中,活动在全局上减弱,并且活动模式和突触结构都以细胞类型特异性的方式发生改变。在大脑中不到 2%的神经元表达 Trpγ。这些神经元在整个大脑中分支,沉默或激活它们会导致大脑活动的丧失或获得。总之,这些结果表明,这一小部分神经元协调大脑的发育活动。我们提出,发育活动的刻板模式是由离散的、基因特异性的网络驱动的,以指导单个细胞和突触水平的神经回路组装。这项工作确立了果蝇大脑作为研究活动如何促进突触和回路形成的实验可处理系统。