P1: Sources and Mechanisms of Sequential Activity

项目摘要/摘要：项目 1，序列活动的来源和机制 在证据积累过程中，顺序活动在小鼠大脑中广泛且占主导地位 决策任务和其他任务也是如此。这种活动可能形成一个“时间支架”，其上还有其他活动 变量被编码在这些连续主动响应的幅度中。此次活动，不同于 通常在感知决策中研究的坡道和持续活动可以由导航驱动。第一个目标 将通过识别产生顺序表示的条件来测试这个想法，例如任务的 时间结构、空间位置导航或视觉刺激。为了区分这些可能性，我们 将记录隔离这些关键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 任务特征消除了顺序活动，产生斜坡或持久性。 第二个目标是使用局部冷却来测试纹状体作为主颞叶的潜在作用。 脚手架。背内侧纹状体（DMS）的中型多棘神经元表现出连续的活动。将此功能失活 提示期的区域对选择有很大的影响，但很少有 DMS 序列在这个时期是特定于选择的。 相反，我们建议 DMS 生成一个时间支架来控制选择的时间和 新皮质和海马体中的证据编码序列。为了检验这个假设，我们将使用焦点冷却 减缓纹状体神经动力学，同时记录新皮质和海马体。这些结果将限制 序列生成模型并揭示序列神经活动的机制基础。 第三个目标是通过构建 具有生成选择序列的三种架构的模型。在移动凹凸吸引子模型中， 群体中的活动地点共同编码位置和证据。在竞争链模型中， 证据以幅度编码，而位置以活动位置编码，在两个竞争序列中。 在位置证据乘法模型中，证据在控制的经典斜坡活动中积累 随着位置依次激活的活动增益。这些模型将使可测试的实验 预测可以帮助我们区分这些网络架构。 第四个目标是将超微结构解剖连接性与神经编码进行比较。我们将使用 行为过程中神经活动的细胞分辨率成像，然后通过连续切片电子显微镜观察 背侧海马和新皮质中的相同神经元，以经验性地测试顺序网络模型 活动。该项目的结果将共同确定任务特征、大脑区域、神经结构和 顺序活动的外观、时间和功能的微观解剖学。我们期望 该项目中的实验和模型将极大地推进 BRAIN 计划的三个优先领域： 大脑在行动，展示因果关系，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.