Resolving the diversity of prefrontal neuron activity within and across behavioral tasks in mice

前额皮质（PFC）神经元的一个显著特征是它们的功能多样性，这可能对它们以适应性和灵活的方式控制行为的能力至关重要。这种多样性体现在两个方面。首先，PFC神经元的活动受到多种认知和行为任务的调节。其次，在任何给定的任务中，PFC神经元表现出各种各样的行为和任务相关的放电模式，这些模式无法轻易表征。当前提案的总体目标是揭示PFC神经元反应多样性的这两个方面的组织原则。首先，我们将研究PFC神经元的任务相关放电模式的多样性在多大程度上可以通过它们不同的投射目标来解释，从而解决该联盟的核心假设2。为此，我们将使用钙成像来比较投射到不同皮层和皮层下区域的PFC神经元与工作记忆相关的活动模式。我们假设投射到不同目标的神经元将显示不同的任务相关反应特性，揭示mPFC向每个下游目标传递的独特信号。我们还将广泛表征投影定义的mPFC种群的解剖组织。其次，我们将研究与PFC相关的不同行为在多大程度上涉及PFC神经元的独立或重叠集合，从而解决该联盟的核心假设1。为此，我们将在小鼠执行多种行为任务（包括工作记忆和感觉决策）时对相同的PFC神经元群进行纵向钙记录。我们假设PFC神经元将被组织成在单个任务中被招募或在多个任务中活跃的集合，反映了共同的神经计算。我们还将研究在不同行为任务的顺序学习过程中，PFC中与任务相关的活动模式和组合是如何动态形成和修改的。因此，通过比较PFC神经元在行为任务和投射目标中的活动，我们希望能够深入了解影响PFC神经元反应多样性的因素，以及它们组成指导灵活行为的整体的组织。

A striking feature of prefrontal cortex (PFC) neurons is their functional diversity, which likely is crucial to their ability to control behavior in an adaptive and flexible manner. This diversity is manifest in two ways. First, the activity of PFC neurons is modulated by a wide variety of cognitive and behavioral tasks. Second, within any given task, PFC neurons display a variety of behavioral and task-related firing patterns that defy easy characterization. The overall goal of the current proposal is to uncover organizing principles underlying these two aspects of response diversity in PFC neurons. First, we will examine to what extent the diversity in task-related firing patterns of PFC neurons can be explained by their different projection targets, addressing core hypothesis 2 of the consortium. To this end, we will use calcium imaging to compare the working memory-related activity patterns of PFC neurons projecting to different cortical and subcortical areas. We hypothesize that neurons projecting to different targets will display different task-related response properties, revealing the unique signals relayed by the mPFC to each of its downstream targets. We will also extensively characterize the anatomical organization of projection-defined mPFC populations. Second, we will examine to what extent different behaviors that have been associated with the PFC engage independent or overlapping ensembles of PFC neurons and thus address core hypothesis 1 of the consortium. To this end, we will perform longitudinal calcium recordings of the same PFC neuron population in mice while they perform multiple behavioral tasks, including working memory and sensory decision-making. We hypothesize that PFC neurons will be organized into ensembles that are recruited either during single tasks or active across multiple tasks, reflecting common neural computations. We will also examine how task-related activity patterns and ensembles in the PFC are dynamically formed and modified during the sequential learning of different behavioral tasks. Thus, by comparing PFC neuronal activity across behavioral tasks and projection targets, we hope to gain insights into the factors that shape the response diversity of PFC neurons and their organization into ensembles guiding flexible behavior.