Specific modulation of local and long-range visual cortical circuits by goal-directed attention

摘要 如果我们不能，世界上可获得的感官信息量将是巨大的 快速、灵活地选择与我们当前需求相关的特定刺激。感觉的内源性控制 处理可以改善感知敏感度和行为性能，并中断 精神疾病中的这些认知机制与行为灵活性的缺陷有关。注意 可能通过调节大脑皮层的活动来使感觉编码更有效 处理这些独特功能的网络。事实上，在视觉皮质区域，当注意力被引导到 神经元的感受野，放电率增加，与其他神经元的协调活动发生变化。 这些发现表明，注意力通过改善大脑传递的信号来提高知觉能力。 特定的神经元池与它们的下游目标相连，以解释视觉场景。此外，由于这些 变化发生在快速的时间尺度上，它们必须由偏向的功能连接性的变化来调节 前馈处理。确定哪些视觉皮层回路迅速改变了它们的活动和连接 注意将需要在生物体中开发的行为任务，在该有机体中，用于监控和 可以使用操控特定神经元亚群的活动。为此，我开发了一种线索，多- 头部固定小鼠的模式注意范式；这将使我能够使用双光子钙成像来监控 当小鼠执行任务时，初级视觉皮质(V1)中的神经元活动。在这个项目中，我将测试 一种假说认为V1神经元的专用子网络通过注意 它们编码的特征。我的初步数据表明，平均而言，V1神经元的反应增加了它们的活动 当视觉刺激与行为相关时。在目标1中，我将确定注意的效果和时间进程 在小鼠V1中进行调制，以检验V1神经元在快速的、试验到试验的时间尺度上被调制的假设。 特征注意可能通过提高反应最好的神经元的信噪比来改善V1的编码 那些特征。在目标2中，我将根据神经元的调谐特性来识别神经元的功能亚群 在任务中使用的视觉刺激，并确定哪些是由注意力特别调制的。在《目标3》中，我会 确定解剖学上定义的群体是否受到注意力的特别调节。在这些 实验中，我将V1轴突终末成像在较高的视觉区域，从而分离出特定的皮质 比较这些不同的处理流在视觉刺激 出席了。后一项实验将揭示注意对视觉处理的影响是如何传递给 影响行为的下游目标。通过开辟新的途径来确定细胞和电路 注意的机制，这个项目将使该领域更接近于了解感觉加工是如何 机器可以被优化以指导感知和行为。

ABSTRACT The amount of sensory information available in the world would be overwhelming if we weren’t able to rapidly and flexibly select specific stimuli that are relevant to our current needs. Endogenous control of sensory processing enables improvements in both perceptual sensitivity and behavioral performance and disruption of these cognitive mechanisms in psychiatric diseases have been linked to deficits in behavioral flexibility. Attention to specific stimulus features may make sensory encoding more efficient by modulating activity in cortical networks that process those unique features. Indeed, in visual cortical areas, when attention is directed toward the receptive field of a neuron, the firing rate increases and coordinated activity with other neurons changes. These findings suggest that attention improves perceptual performance by improving the signal carried by specific pools of neurons to their downstream targets for interpreting the visual scene. Additionally, since these changes occur on a rapid timescale, they must be mediated by changes in the functional connectivity that bias feed-forward processing. Determining which visual cortical circuits rapidly change their activity and connectivity with attention will require a behavioral task developed in an organism in which tools for monitoring and manipulating activity in specific subsets of neurons can be used. To this end, I have developed a cued, multi- modal attention paradigm for head-fixed mice; this will allow me to use two-photon calcium imaging to monitor neuronal activity in the primary visual cortex (V1) as the mouse performs the task. In this project I will test the hypothesis that specialized subnetworks of V1 neurons are rapidly and selectively modulated by attention to the features they encode. My preliminary data suggests that V1 neuron responses, on average, increase their activity when visual stimuli are behaviorally relevant. In Aim 1, I will determine the effect and time-course of attentional modulation in mouse V1 to test the hypothesis that V1 neurons are modulated on a rapid, trial-to-trial timescale. Feature attention may improve encoding in V1 by increasing the signal-to-noise of neurons that respond best to those features. In Aim 2, I will identify functional subgroups of neurons based on their tuning properties to the visual stimuli used in the task, and determine which are specifically modulated by attention. In Aim 3, I will determine whether anatomically defined populations are specifically modulated by attention. In these experiments, I will image V1 axon terminals in the higher visual areas, thus isolating specific cortico-cortical projections to compare if these different processing streams change their activity when visual stimuli are attended. This latter experiment will reveal how the effects of attention on visual processing are passed on to downstream targets to affect behavior. By opening new avenues for determining the cellular and circuit mechanisms of attention, this project will bring the field closer to understanding how sensory processing machinery can be optimized to guide perception and behavior.