Department of Biological Sciences, Vanderbilt University and Medical Center, Nashville, TN, 37235, USA.
Department of Cell and Developmental Biology, Vanderbilt University and Medical Center, Nashville, TN, 37235, USA.
Sci Rep. 2024 Apr 20;14(1):9110. doi: 10.1038/s41598-024-59942-3.
Critical periods are temporally-restricted, early-life windows when sensory experience remodels synaptic connectivity to optimize environmental input. In the Drosophila juvenile brain, critical period experience drives synapse elimination, which is transiently reversible. Within olfactory sensory neuron (OSN) classes synapsing onto single projection neurons extending to brain learning/memory centers, we find glia mediate experience-dependent pruning of OSN synaptic glomeruli downstream of critical period odorant exposure. We find glial projections infiltrate brain neuropil in response to critical period experience, and use Draper (MEGF10) engulfment receptors to prune synaptic glomeruli. Downstream, we find antagonistic Basket (JNK) and Puckered (DUSP) signaling is required for the experience-dependent translocation of activated Basket into glial nuclei. Dependent on this signaling, we find critical period experience drives expression of the F-actin linking signaling scaffold Cheerio (FLNA), which is absolutely essential for the synaptic glomeruli pruning. We find Cheerio mediates experience-dependent regulation of the glial F-actin cytoskeleton for critical period remodeling. These results define a sequential pathway for experience-dependent brain synaptic glomeruli pruning in a strictly-defined critical period; input experience drives neuropil infiltration of glial projections, Draper/MEGF10 receptors activate a Basket/JNK signaling cascade for transcriptional activation, and Cheerio/FLNA induction regulates the glial actin cytoskeleton to mediate targeted synapse phagocytosis.
关键期是指在生命早期的一段特定时间内，感官体验重塑突触连接，以优化环境输入。在果蝇的幼脑发育过程中，关键期的经验驱动着突触的消除，而这种消除是暂时可逆的。在与投射神经元（延伸到大脑学习和记忆中心）相连接的单一嗅觉感觉神经元（OSN）类中，我们发现胶质细胞介导了 OSN 突触小体在关键期气味暴露后的经验依赖性修剪。我们发现胶质细胞突起会在关键期经验的刺激下渗透到脑神经丛中，并利用 Draper（MEGF10）吞噬受体来修剪突触小体。在下游，我们发现 Basket（JNK）和 Puckered（DUSP）信号通路拮抗作用对于激活的 Basket 向胶质细胞核内的易位是必需的。依赖于这种信号通路，我们发现关键期经验会驱动 Cheerio（FLNA）这种与 F-actin 相连的信号支架的表达，这对于突触小体的修剪是绝对必需的。我们发现 Cheerio 介导了胶质细胞 F-actin 细胞骨架的经验依赖性调节，以实现关键期重塑。这些结果定义了一个在严格定义的关键期内，经验依赖性大脑突触小体修剪的连续途径；输入经验驱动神经丛中胶质细胞突起的渗透，Draper/MEGF10 受体激活 Basket/JNK 信号级联反应，以实现转录激活，而 Cheerio/FLNA 的诱导调节胶质细胞肌动蛋白细胞骨架，以介导靶向性突触吞噬作用。
