Department of Neurobiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Neuroscience Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Neurobiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Curr Biol. 2021 Aug 9;31(15):3248-3261.e3. doi: 10.1016/j.cub.2021.05.018. Epub 2021 Jun 8.
Sleep is essential for a variety of plastic processes, including learning and memory. However, the consequences of insufficient sleep on circuit connectivity remain poorly understood. To better appreciate the effects of sleep loss on synaptic connectivity across a memory-encoding circuit, we examined changes in the distribution of synaptic markers in the Drosophila mushroom body (MB). Protein-trap tags for active zone components indicate that recent sleep time is inversely correlated with Bruchpilot (BRP) abundance in the MB lobes; sleep loss elevates BRP while sleep induction reduces BRP across the MB. Overnight sleep deprivation also elevated levels of dSyd-1 and Cacophony, but not other pre-synaptic proteins. Cell-type-specific genetic reporters show that MB-intrinsic Kenyon cells (KCs) exhibit increased pre-synaptic BRP throughout the axonal lobes after sleep deprivation; similar increases were not detected in projections from large interneurons or dopaminergic neurons that innervate the MB. These results indicate that pre-synaptic plasticity in KCs is responsible for elevated levels of BRP in the MB lobes of sleep-deprived flies. Because KCs provide synaptic inputs to several classes of post-synaptic partners, we next used a fluorescent reporter for synaptic contacts to test whether each class of KC output connections is scaled uniformly by sleep loss. The KC output synapses that we observed here can be divided into three classes: KCs to MB interneurons; KCs to dopaminergic neurons; and KCs to MB output neurons. No single class showed uniform scaling across each constituent member, indicating that different rules may govern plasticity during sleep loss across cell types.
睡眠对于各种塑性过程都是必不可少的，包括学习和记忆。然而，睡眠不足对电路连接的后果仍知之甚少。为了更好地了解睡眠剥夺对记忆编码电路中突触连接的影响，我们研究了在果蝇蘑菇体（MB）中突触标记物分布的变化。活性区成分的蛋白陷阱标签表明，最近的睡眠时间与 MB 叶中 Bruchpilot（BRP）的丰度呈反比；睡眠剥夺会增加 BRP，而诱导睡眠则会降低整个 MB 中的 BRP。一夜的睡眠剥夺也会增加 dSyd-1 和 Cacophony 的水平，但不会增加其他的突触前蛋白。细胞类型特异性的遗传报告显示，MB 内在的 Kenyon 细胞（KCs）在睡眠剥夺后整个轴突叶中表现出突触前 BRP 的增加；在从大的中间神经元或多巴胺神经元向 MB 投射的过程中没有检测到类似的增加，这些神经元支配 MB。这些结果表明，KCs 中的突触前可塑性是睡眠剥夺后 MB 叶中 BRP 水平升高的原因。由于 KCs 向几个类别的突触后伴侣提供突触输入，我们接下来使用突触接触的荧光报告来测试每个 KC 输出连接是否因睡眠剥夺而均匀缩放。我们在这里观察到的 KC 输出突触可以分为三类：KCs 到 MB 中间神经元；KCs 到多巴胺神经元；和 KCs 到 MB 输出神经元。没有一个类别在每个组成成员中表现出均匀的缩放，这表明不同的规则可能在不同的细胞类型中控制着睡眠剥夺期间的可塑性。
