P1: Sources and Mechanisms of Sequential Activity

项目摘要/摘要：项目1，顺序活动的来源和机制 在证据积累期间，顺序活动在小鼠大脑中广泛存在并占主导地位 决策任务，以及在其他任务中。这样的活动可能形成一个“临时的脚手架”，在这个脚手架上的其他人 变量以这些顺序激活的响应的幅度进行编码。此活动不同于 坡道和持续活动通常在知觉决策中被研究，可以由导航驱动。第一个目标 将通过识别产生顺序表示的条件来测试这一想法，例如任务的 计时结构、空间位置导航或视觉刺激。为了区分这些可能性，我们 将记录在分离这些键的任务期间包含顺序活动的区域的神经活动 特点：主动导航、被动导航、视觉刺激。这项工作将确定是否移除 任务功能的使用消除了顺序活动，从而产生渐变或持续性。 第二个目标将是使用焦点冷却来测试纹状体作为主要颞叶的潜在作用。 脚手架。背内侧纹状体(DMS)的中棘神经元呈顺序性活动。停用此功能 提示期的区域对选择有很大的影响，但很少有DMS序列在这一时期具有选择专一性。 相反，我们建议DMS生成一个时间脚手架，控制选择的时间和 大脑皮层和海马区的证据编码序列。为了验证这一假设，我们将使用焦点冷却 减慢纹状体神经动力学，同时记录新皮质和海马区。这些结果将约束 序列生成的模型，并揭示序列神经活动的机制基础。 第三个目标将是识别可能支撑观测数据的网络体系结构，方法是 具有三个架构的模型，可生成可供选择的序列。在运动凹凸吸引子模型中， 人口中的活动地点联合编码位置和证据。在竞争链模型中， 证据在两个相互竞争的序列中以幅度编码，而位置以活动位置编码。 在位置-证据乘法模型中，证据是在控制 按位置顺序激活的活动的增益。这些模型将成为可测试的实验模型 帮助我们区分这些网络架构的预测。 第四个目标是比较超微结构的解剖学连通性和神经编码。我们将使用 行为过程中神经活动的细胞分辨率成像，随后是连续切片电子显微镜 相同的神经元在背侧海马区和新皮质，以经验性地测试网络模型的序列 活动。总而言之，这个项目的结果将确定任务特征、大脑区域、神经架构和 连续活动的外观、时间和功能的微尺度解剖学。我们预计， 该项目中的实验和模型将大大推进大脑倡议的三个优先领域： 大脑在活动，演示因果关系，并确定基本原则。

Project Summary/Abstract: Project 1, Sources and Mechanisms of Sequential Activity Sequential activity is widespread and predominant across the mouse brain during an evidence-accumulation decision task and in other tasks as well. Such activity may form a “temporal scaffold,” on top of which other variables are encoded in the amplitude of these sequentially active responses. This activity, different from the ramps and persistent activity often studied in perceptual decisions, could be driven by navigation. The first aim will be to test this idea by identifying conditions that produce sequential representations, such as the task’s timing structure, navigation through spatial locations, or visual stimulation. To distinguish these possibilities, we will record neural activity from regions containing sequential activity during tasks that isolate these key features: active navigation, passive navigation, and visual stimulation. This work will establish whether removal of task features eliminates sequential activity, producing ramps or persistence. The second aim will be to use focal cooling to test a potential role of the striatum as a master temporal scaffold. Medium spiny neurons of dorsal medial striatum (DMS) show sequential activity. Inactivation of this region in the cue period has large effects on choice, yet few DMS sequences are choice-specific in this period. We propose instead that DMS generates a temporal scaffold that controls the timing of choice and evidence-encoding sequences in neocortex and hippocampus. To test this hypothesis, we will use focal cooling to slow striatal neural dynamics, while recording in neocortex and hippocampus. These results will constrain models of sequence generation and reveal the mechanistic foundations of sequential neural activity. The third aim will be to identify network architectures that could underlie the observed data, by building models with three architectures that generate choice-selective sequences. In the moving bump attractor model, activity location in a population jointly encodes position and evidence. In the competing-chains model, evidence is encoded in amplitude, while position is encoded in activity location, in two competing sequences. In the position-evidence multiplicative model, evidence is accumulated in classic ramping activity that controls the gain of activity that is sequentially activated with position. These models will make testable experimental predictions to help us distinguish these network architectures. The fourth aim will be to compare ultrastructural anatomical connectivity with neural coding. We will use cellular-resolution imaging of neural activity during behavior, followed by serial-section electron microscopy of the same neurons in the dorsal hippocampus and neocortex, to empirically test network models of sequential activity. Together, the results of this project will identify task features, brain regions, neural architectures, and microscale anatomy underlying the appearance, timing, and function of sequential activity. We expect that the experiments and models in this project will substantially advance three priority areas of the BRAIN Initiative: the brain in action, demonstrating causality, and identifying fundamental principles.