Role of the Superior Colliculus in Orienting Eye Movements during REM Sleep

项目摘要/摘要 REM睡眠伴随着以生动视觉体验为特征的梦，这显然表明 我们的大脑拥有一个关于世界的生成模型。越来越多的研究表明，我们感知世界 通过这样一种生成模式和该模式的异常表达，可以为某些精神疾病 精神错乱。因此，了解我们的大脑如何支持生成模型是很重要的。这样做的目的是 项目是通过集中于神经元来阐明发生模型的神经生理学基础。 快速眼动睡眠期间的活动，在此期间，大脑的生殖模型与外部世界分离。 在奖项的指导阶段，我首先建议研究快速眼球运动，作为对 快速眼动睡眠中的生殖模式。快速眼动睡眠中的快速眼球运动被认为是 梦的虚拟视觉环境的主动采样。然而，这一假设没有得到以下方面的支持 生理证据。为了提供生理学证据来检验这一假说，我将重点放在 头部方向(HD)细胞，编码动物相对于环境的HD。活动模式 在快速眼动睡眠期间观察到的HD细胞的数量与在清醒时观察到的相似。这使得解码成为可能 快速眼动睡眠期间的虚拟高清。我将测试快速眼动睡眠中的快速眼球运动是否可以预测变化 从记录在丘脑前背侧的HD细胞中解码。为了实现这个目标，我将结合大型 大规模电生理记录、先进的解码方法和小型化的眼睛跟踪系统。 在R00阶段，我建议研究上丘(SC)作为虚拟 快速眼动睡眠时头部朝向和快速眼球运动。SC是大脑和眼睛的重要枢纽 在清醒的动物中定位。我将测试Sc在快速眼动睡眠期间的自发活动是否可以预测 通过同时记录SC和丘脑前背侧的神经元活动改变虚拟HD 以及监测眼球的快速运动。我将进一步测试SC活动对虚拟环境的因果影响 在快速眼动睡眠期间，通过激活和停用SC来调整头部方向和快速眼球运动。 总而言之，这个项目将提供对神经生理学的新见解，了解 世界的生成模型和我们与它的互动是在快速眼动睡眠期间组织起来的。这将构成 关键一步，了解我们是如何通过内部模型来看待世界的，以及反常的表达是如何 该模型可能是精神分裂症等一些精神疾病的发病机制的基础。 我将在该奖项的培训期间获得的技术和科学专业知识将是至关重要的 在我自己的独立实验室建立了研究计划的基础，重点是SC在 在快速眼动睡眠中协调生殖模型。除此之外，密集的职业发展培训， 来自指导团队的指导，以及 加州大学旧金山分校的神经科学界将确保我成功地转变为一名独立的调查员。

PROJECT SUMMARY/ ABSTRACT REM sleep is accompanied by dreams characterized by vivid visual experience, which evidently indicates that our brain holds a generative model of the world. Converging studies suggest that we perceive the world through such a generative model and the abnormal expression of the model could underlie some psychiatric disorders. Thus, it is important to understand how our brain supports the generative model. The goal of this project is to elucidate the neurophysiological basis for the generative model by focusing on the neuronal activity during REM sleep, during which the brain’s generative model is detached from the external world. In the mentored phase of the award, I first propose to investigate rapid eye movements as a readout of the generative model during REM sleep. Rapid eye movements during REM sleep are proposed to represent active sampling of the virtual visual environment of dreams. However, this hypothesis is poorly supported by physiological evidence. To provide physiological evidence to test the hypothesis, I will focus on the activity of the head direction (HD) cells, which code for the animals’ HD relative to the environment. The activity pattern of HD cells during REM sleep is similar to what is observed during wake. This makes it possible to decode virtual HD during REM sleep. I will test whether rapid eye movements during REM sleep can predict changes in HD decoded from HD cells recorded in the anterodorsal thalamus. To achieve this goal, I will combine large scale electrophysiological recordings, advanced decoding methods, and miniaturized eye tracking systems. In the R00 phase, I propose to investigate the superior colliculus (SC) as the neuronal substrate for virtual head orienting and rapid eye movements during REM sleep. The SC is an important hub for head and eye orienting in awake animals. I will test whether spontaneous activity in the SC during REM sleep predicts changes in virtual HD by simultaneously recording neuronal activity in the SC and in the anterodorsal thalamus as well as monitoring rapid eye movements. I will further test the causal impact of the SC activity on virtual head orienting and rapid eye movements by activating and inactivating the SC during REM sleep. In summary, this project will provide new insights into the neurophysiological understanding of how the generative model of the world and our interaction with it is organized during REM sleep. This will constitute the critical step to understand how we see the world through the internal model and how the abnormal expression of the model could underlie the pathogenesis of some psychiatric disorders such as schizophrenia. The technical and scientific expertise that I will acquire during the training period of the award will be crucial for setting the basis of research programs in my own independent laboratory focusing on the role of the SC in orchestrating the generative model during REM sleep. In addition to this, intense career development training, the guidance from the mentoring team, as well as the collaboration and the rich intellectual interaction in the UCSF neuroscience community will ensure my successful transition into an independent investigator.