Regulation of Intrinsic Plasticity in Neural Circuits

慢性睡眠剥夺的认知效应对公共健康和经济的影响， 随着我们社会日益全球化和24小时的性质， 几十亿然而，尽管如此，我们对睡眠影响的机制知之甚少。 记忆电路记忆的形成对睡眠水平是双向敏感的。睡在颞叶 窗口跟踪训练能促进记忆的形成，而睡眠剥夺则对记忆的形成有负面影响。 影响其形成。此外，研究表明，学习可以增强睡眠动力，这表明， 在记忆形成过程中有内在的机制促进睡眠。在果蝇中， 非常详细地了解记忆形成和睡眠回路的基础过程。 该提案利用这一知识，首次在细胞水平上理解了直接的 记忆和睡眠系统之间的联系。 在目标1中，我们将剖析协作网络中协同传输的组织和功能 神经元，一种对长期记忆形成和学习依赖性睡眠至关重要的细胞类型。这些 细胞释放多个发射器，并了解这些发射器如何部署在电路中， 对理解它们的功能很重要。 在目标2中，我们探讨了在脑内共递质释放的调节和可塑性。我们 假设两个发射器的目标选择性释放在时间上施加差异， 这将对电路中的计算产生深远的影响。 在目标3中，我们问共传输如何影响电路动态。我们面临的核心挑战 今天，我们对睡眠和记忆形成的理解是了解电路的动力学。 在这个目标中，我们使用功能成像来映射MB回路中的时间关系以及 在他们的规则。 理解这一点，细胞的功能机制将提供重要的原则 这将导致设计策略来对抗睡眠剥夺的负面认知影响。

The public health and economic impact of the cognitive effects of chronic sleep deprivation have grown enormously with the increasingly global and 24 hour nature of our society, and costs are in the billions. In spite of this, however, we know very little about the mechanisms by which sleep influences memory circuits. Memory formation is bidirectionally sensitive to sleep levels. Sleep in the temporal window following training can enhance formation of memory, while sleep deprivation has negative effects on its formation. In addition, learning has been shown to enhance sleep drive, suggesting that there are intrinsic mechanisms to promote sleep during memory formation. In Drosophila, we have a very detailed understanding both of the processes that underlie memory formation and sleep circuits. This proposal leverages this knowledge to understand, for the first time at a cellular level, the direct links between memory and sleep systems. In Aim 1 we will dissect the organization and functionality of co-transmission in the DPM neurons, a cell type critical for both long-term memory formation and learning-dependent sleep. These cells release multiple transmitters and understanding how these transmitters are deployed in the circuit will be important for understanding their functions. In Aim 2 we probe the regulation and plasticity of co-transmitter release in DPM. We hypothesize that target-selective release of the two transmitters imposes differences in the timing and amplitude of signals which will have profound effects on computations in the circuit. In Aim 3 we ask how co-transmission affects circuit dynamics. The core challenge we face today in our understanding of sleep and memory formation is to understand the dynamics of the circuit. In this aim we use functional imaging to map the temporal relationships in the MB circuit and the role of DPM in their regulation. Understanding this the cellular mechanisms of DPM function will provide important principles that will lead to the design of strategies to combat the negative cognitive effects of sleep deprivation.