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

摘要 如果我们不能从我们的大脑中 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 处理能够改善感知灵敏度和行为表现， 精神疾病中的这些认知机制与行为灵活性的缺陷有关。关注 特定的刺激特征可能会使感觉编码更有效，通过调节皮层的活动， 处理这些独特特征的网络。事实上，在视觉皮层区域，当注意力指向 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，注意力通过改善信号来改善感知性能。 特定的神经元池到它们的下游目标，用于解释视觉场景。此外，由于这些 变化发生在一个快速的时间尺度上，它们必须通过功能连接的变化来介导， 前馈处理确定哪些视觉皮层回路快速改变其活动和连接 需要在有机体中开发出一种行为任务，其中用于监测和 可以使用操纵特定神经元子集中的活动。为此，我开发了一个多功能的，多... 头部固定小鼠的模态注意范式;这将允许我使用双光子钙成像来监测 当小鼠执行任务时，初级视觉皮层（V1）中的神经元活动。在这个项目中，我将测试 V1神经元的专门子网络被注意力快速和选择性地调节， 它们编码的特征。我的初步数据表明，平均而言，V1神经元的反应会增加它们的活性， 当视觉刺激与行为相关时。在目标1中，我将确定注意力的效果和时间过程。 在小鼠V1的调制，以测试的假设，即V1神经元调制的快速，试验到试验的时间尺度。 特征注意力可以通过增加最佳响应的神经元的信噪比来改善V1中的编码。 这些特征。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分组。 任务中使用的视觉刺激，并确定哪些是专门由注意调制。在目标3中，我将 确定解剖学定义的人群是否受到注意力的特别调节。在这些 实验中，我将图像V1轴突终端在更高的视觉领域，从而隔离特定的皮质-皮质 投射来比较这些不同的处理流是否在视觉刺激被 出席了后一个实验将揭示注意力对视觉处理的影响是如何传递给 下游目标来影响行为。通过开辟新的途径来确定细胞和电路 注意力的机制，这个项目将使该领域更接近理解感觉处理如何 机器可以被优化以引导感知和行为。

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.