Combining Vision with Action one Synapse from the Eye

离眼睛一个突触的地方是一个基本的大脑结构——上丘，它负责整合感觉输入，将注意力分配到空间位置，并产生头部和身体对这些位置的定向运动。来自眼睛的输入进入上丘（sSC）的表面部分，该部分被认为主要包含对外部世界的视觉表征。然而，我们实验室最近的观察表明，sSC的作用远不止单纯的视觉：它的视觉反应强烈地受到非感官信号的影响。该项目将揭示这个关键的大脑区域如何将视觉信号与反映大脑和行为状态、决策过程和运动动作的非感觉信号结合起来。此外，它将有助于揭示非感觉信号的来源，并提供视觉和非感觉信号结合的功能效果的简单模型，以及潜在的神经回路。为了实现这些目标，我们将利用我们在实验室开发的新的神经成像和行为技术。我们将使用双光子成像来记录清醒小鼠sSC内数百个基因鉴定神经元的活动。同样的技术将揭示那些来自眼睛或大脑皮层的神经元的输入活动。这些成像测量将在小鼠被动观看刺激或主动执行视觉任务时进行。我们的第一个目标是关注sSC如何受到大脑和行为状态（如觉醒和运动）的影响。我们将成像sSC对一系列视觉刺激的反应，并将其与瞳孔直径反映的觉醒水平和运动联系起来。初步数据表明，这些因素对一些细胞的反应有很大的影响，而对另一些细胞的影响可以忽略不计。我们将区分细胞类别，将这些效应映射到sSC的电路上。我们的第二个目标关注的是在视觉刺激用于特定决策和行动的互动条件下，sSC是如何受到影响的。当动物执行需要目标导向运动的视觉任务时，我们将对sSC中的不同细胞类别进行成像。我们将使用简单的相关测量和神经反应的预测模型将刺激、表现和动作的反应联系起来。这些数据将描述sSC如何将视觉信号与与决策和行动有关的信号结合起来。我们的第三个目标集中在向sSC提供非感觉信号的源和电路上。sSC的主要视觉输入来自眼睛和大脑皮层。为了评估它们在提供视觉和非感觉信号方面的作用，我们将成像它们在sSC中的轴突末梢的活动以及投射到sSC的皮质神经元的活动。然后我们会让大脑皮层失活来揭示它对大脑皮层的影响。结果将表征sSC从眼睛和皮层继承的信号，并将表明后者是否有必要解释sSC中所见的视觉和非感觉信号的组合。所有目标的结果将使我们能够为sSC中视觉和非感觉信号的组合建立简单的功能和电路模型。这些实验有可能改变我们对大脑如何整合感觉和非感觉输入的看法，展示神经元如何从眼睛获得直接输入，将视觉信号与与大脑和行为状态、决策和行动相关的信号结合起来。扩大我们对上丘功能和回路的理解，最终将使我们能够模拟和复制这个大脑区域如何将感觉输入转化为分配注意力和产生行动的命令。它还可能有助于了解疾病中的注意力缺陷，并开发治疗方法。

One synapse away from the eye lies a fundamental brain structure, the superior colliculus, responsible for integrating sensory input, allocating attention to spatial locations, and generating orienting movements of the head and body to those locations. The inputs from the eye go to the superficial portion of the superior colliculus (sSC), which is thought to contain a mostly visual representation of the external world. Recent observations in our laboratory, however, suggest that sSC does much more than pure vision: its visual responses are strongly shaped by non-sensory signals. The proposed project will reveal how this key brain region combines visual signals with non-sensory signals reflecting brain and behavioral state, decision processes and motor actions. Further, it will help reveal the sources of non-sensory signals, and provide a simple model of the functional effects of this combination of visual and non-sensory signals, and of the underlying neural circuits. To achieve these goals, we will leverage novel neural imaging and behavioral techniques that we have developed in our laboratory. We will use two-photon imaging to record activity of hundreds of genetically identified neurons within the sSC of awake mice. The same technique will reveal the activity of the inputs to those neurons originating in the eye or in the cerebral cortex. These imaging measurements will be made while mice are passively viewing a stimulus or actively performing a visual task. Our first objective focuses on how sSC is affected by brain and behavioral state such as arousal and locomotion. We will image responses in sSC to a range of visual stimuli and relate them to the level of arousal, as reflected by pupil diameter, and to locomotion. Preliminary data indicate that these factors have an enormous effect on the responses of some cells and a negligible one on others. We will distinguish cell classes to map these effects onto the circuits of sSC. Our second objective focuses on how sSC is affected in interactive conditions where visual stimuli are used for specific decisions and actions. We will image different cell classes in the sSC while the animal performs a visual task requiring a goal-directed movement. We will relate responses to stimulus, performance, and action using simple correlation measures and a predictive model of neural responses. The data will characterize how the sSC combines visual signals with signals related to decision and action.Our third objective focuses on the sources and circuits that provide the sSC with non-sensory signals. The main visual inputs to sSC originate from the eye and from the cerebral cortex. To assess their role in providing visual and non-sensory signals, we will image the activity of their axon terminals in sSC and the activity of cortical neurons projecting to the sSC. We will then inactivate the cortex to reveal its effect on sSC. The results will characterize the signals that sSC inherits from the eye and from the cortex, and will indicate if the latter is necessary to explain the combination of visual and non-sensory signals seen in sSC. Results from all objectives will allow us to build simple functional and circuit models for the combination of visual and non-sensory signals in the sSC.These experiments have the potential to change the way we think about how the brain integrates sensory and non-sensory inputs, showing how neurons getting direct input from the eye combine visual signals with signals related to brain and behavioural state, decisions, and actions.Expanding our understanding of the function and circuitry of the superior colliculus will eventually enable us to simulate and replicate how this brain area transforms sensory input into commands that allocate attention and generate actions. It may also help to understand attentional deficits in disease and develop cures and therapies.