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

项目摘要/摘要 神经回路的持续活动支持多种大脑功能，从运动控制到导航再到 感性的决策。相关研究表明，持续活动模式在 不同的行为，表明各个电路根据上下文执行灵活的计算 正在进行的大脑活动和运动功能。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力学的技术限制，因此很难实现。一个容易驯服的人 克服这一挑战的系统是斑马鱼，一种脊椎动物模式生物，具有光学可及 通过激光显微镜，可以同时进行钙成像和光遗传刺激的大脑。研究领域 我们的实验室专注于斑马鱼动眼运动积分器，这是一个参与凝视自适应控制的后脑回路。 位置。这种电路产生持续的活动，直接驱动容易量化的运动行为。在之前 工作中，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，但尚不清楚这些上下文相关的动力学如何有助于眼球运动控制以及如何 它们与复杂行为的发展有关。在拟议的研究中，我将同时进行 双光子成像和光发生刺激在视觉运动行为中确定不同的模式 积分器动力学对不同类型的眼球运动有贡献。首先，我会收集一个全面的 斑马鱼幼体和幼鱼全脑神经活动的纵向数据集 眼球运动行为，测试积分器中持续模式的数量是否确实随着 行为曲目。然后，我将在单点进行积分网络的实时闭环模拟。 细胞分辨率，引导特定活动模式的电路动力学，以测试它们对电机的因果影响 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.