Elucidating the role of the oculomotor circuit in free viewing visual search

项目摘要 近50年来，科学家们一直在研究眼动控制和活动之间的关系 前视野区(FEF)、上丘(SC)和顶内区外侧区(LIP)的神经元。这位将军 这些研究的结果是，这三个区域的神经元对眼动行为都很重要， 但他们发现这两个地区之间的差异很小，这意味着它们都做着相似的事情。最近， 少数实验室已经开始使用更自然的自由观看行为任务，并发现了一种 这些区域的神经反应的实质性差异的数量，表明它们各自发挥着 独特的角色。基于这些数据，我们形成了关于每个区域的作用以及它们如何可能 发挥网络的作用，以产生行为。简单地说，我们已经提出了LIP充当简单的优先级映射 始终可访问，FEF活动控制扫视的时间，SC活动代表最终决策 关于去哪里找。此外，FEF中的一个神经元子集跟踪动物看过的地方。建房 在这项先前的工作中，目前的提案有两个主要目标。第一个是填补我们知识的两个空白 这对最终确定我们的假设是至关重要的。作为这一目标的一部分，我们建议从干细胞神经元中记录 自由观看视觉搜寻任务，以确认SC活动不受正在进行的搜索中的刺激身份的影响。 我们还建议在任务的一个更自然的版本中记录FEF神经元，以确保 我们以前在维持注视过程中看到的抑制是一种控制眼睛时机的机制 运动，而不是与奖励期望相关的机制。这些研究的结果将得到完善。 我们的假设，并为提案的第二个主要目标做好准备，即测试我们的假设是否 角色在功能上是有效的。第二个目标分为三个部分。在每一种情况下，我们都将对各个方面进行因果测试 我们的假设。在第一个实验中，我们将在不同的时间微刺激嘴唇，以测试是否 我们在FEF中发现的抑制控制着从嘴唇到引导眼跳的信息流。在第二个 实验中，我们将停用LIP，同时从FEF和SC进行录制。这项实验的结果将检验 假设嘴唇活动通过FEF和SC驱动眼跳行为，如果不是，这些记录应该 确定哪个区域在引导行为方面确实起到了作用。在第三个实验中，我们将停用FEF，同时 从SC录制。这将允许我们测试我们假设的另外三个方面：FEF活动是否 引导行为以及这是否也在SCI中表示；跟踪信号在FEF中是否在功能上 相关；以及FEF中的活动是否参与控制眼跳的暂时性流动。这些结果 将解决一个长达数十年的问题，即为什么我们有多个大脑区域，因为它提供了一个明确的迹象 LIP、FEF和SC在日常视觉行为中扮演着重要角色。考虑到广泛范围内的患者 神经系统疾病有异常的眼动行为，这些结果可能有助于 药理学或行为学方法来解决这些问题。

Project Summary For almost 50 years, scientists have investigated the relationship between eye movement control and the activity of neurons in the frontal eye field (FEF), superior colliculus (SC) and lateral intraparietal area (LIP). The general findings of these studies have been that neurons in all three areas are important for eye movement behavior, but they have identified very few differences between the areas, implying that they all do similar things. Recently, a small number of labs have started using more naturalistic free-viewing behavioral tasks and have found a number of substantive differences in neural responses across these areas, suggesting that they each play a unique role. Based on these data, we formed a hypothesis about the roles of each area and how they may function as a network to generate behavior. Briefly, we have proposed that LIP acts as simple priority map that is constantly accessible, FEF activity controls the timing of saccades and SC activity represents the final decision about where to look. In addition, a subset of neurons in FEF keeps track of where the animal has looked. Building on this previous work, the current proposal has two main aims. The first is to fill in two gaps of our knowledge that are essential in finalizing our hypothesis. As part of this aim, we propose to record from SC neurons in a free viewing visual foraging task to confirm that SC activity is not affected by stimulus identity in ongoing search. We also propose to record from FEF neurons in an even more natural version of our task to make sure that suppression we have previously seen during maintained fixation is a mechanism for controlling the timing of eye movements as opposed to a mechanism related to reward expectation. The results of these studies will refine our hypothesis and set us up for the second main aim of the proposal, which is to test whether our hypothesized roles are functionally valid. This second aim is broken into 3 components. In each, we will causally test aspects of our hypothesis. In the first experiment, we will microstimulate LIP at different times to test whether the suppression we have identified in FEF controls the flow of information from LIP to guide saccades. In the second experiment, we will inactivate LIP while recording from FEF and SC. The results of this experiment will test the hypothesis that LIP activity drives saccadic behavior via FEF and SC and, if it does not, these recordings should identify which area does play a role in guiding behavior. In the third experiment, we will inactivate FEF while recording from SC. This will allow us to test three additional aspects of our hypothesis: whether FEF activity guides behavior and whether this is also represented in SCI; whether the tracking signal in FEF in functionally relevant; and whether the activity in FEF is involved in controlling the temporal flow of saccades. These results will solve a decades-long question of why we have multiple brain areas by providing a clear indication of what the roles of LIP, FEF and SC are in everyday visual behavior. Given that patients across a broad spectrum of neurological diseases have abnormal eye movement behavior, these results may aid in the development of pharmacological or behavioral methods to combat these problems.