The development of multimodal dynamics in a short-term memory system

项目总结/摘要 神经回路中的持续活动支持从运动控制到导航， 知觉决策相关性研究表明，在持续的活动模式， 不同的行为，这表明各个电路根据上下文执行灵活的计算 大脑活动和运动功能的持续性然而，确定这种变异性的因果意义 由于现有工具中用于精确操纵电路动态特性的技术限制，易处理 克服这一挑战的系统是斑马鱼，一种脊椎动物模式生物， 大脑，允许同时钙成像和光遗传学刺激与激光显微镜。研究 我们的实验室专注于斑马鱼的眼神经整合器，一种参与凝视自适应控制的后脑回路 位置这个回路产生持续的活动，直接驱动容易量化的运动行为。于过往 我们的实验室发现，不同的整合活动模式与不同类型的眼睛有关 运动，但目前还不清楚这些上下文相关的动态如何有助于眼控制，以及如何 它们与复杂行为的发展有关。在本次研究中，我将同时进行 双光子成像和光遗传学刺激在视觉行为，以确定如何不同的模式 积分器动态的不同类型的眼球运动。首先，我将收集一份全面的 在一个广泛的时间范围内， 视觉行为，测试集成器中的持久模式的数量是否确实随着 行为系统然后，我将执行实时闭环模拟的积分器网络在单- 细胞分辨率，沿沿着特定活动模式引导电路动态，以测试它们对运动的因果影响 产出这项研究将提高我们对记忆电路灵活控制的理解，并建立新的 精确操纵网络动态的范例。

PROJECT SUMMARY / ABSTRACT Persistent activity in neural circuits supports a variety of brain functions from motor control to navigation to perceptual decision-making. Correlational studies show significant variation in persistent activity patterns during different behaviors, suggesting that individual circuits perform flexible computations that depend on the context of ongoing brain activity and motor functioning. However, establishing the causal significance of this variability is difficult due to technical limitations in existing tools for precisely manipulating circuit dynamics. A tractable system for overcoming this challenge is the zebrafish, a vertebrate model organism with an optically accessible brain that allows simultaneous calcium imaging and optogenetic stimulation with laser microscopy. Research in our lab focuses on the zebrafish oculomotor integrator, a hindbrain circuit involved in adaptive control of gaze position. This circuit generates persistent activity that directly drives easily quantified motor behavior. In prior work, our lab found that different patterns of integrator activity are associated with distinct types of eye movements, but it is unclear how these context-dependent dynamics contribute to oculomotor control and how they relate to the development of sophisticated behavior. In the proposed research, I will conduct simultaneous two-photon imaging and optogenetic stimulation during visuomotor behavior to determine how different patterns of integrator dynamics contribute to different types of eye movements. First, I will collect a comprehensive longitudinal dataset of brain-wide neural activity in the larval and juvenile zebrafish during a broad range of oculomotor behaviors, testing if indeed the number of persistent patterns in the integrator expands with the behavioral repertoire. Then, I will perform real-time closed-loop stimulation of the integrator network at single- cell resolution, steering circuit dynamics along specific patterns of activity to test their causal impact on motor outputs. This research will improve our understanding of flexible control by memory circuits and establish new paradigms for precise manipulation of network dynamics.