The impact of behavioral state and spatial attention on sensory responses in the primary visual thalamus

项目摘要/摘要 虽然在过去的十年里，在理解感觉反应是如何的方面取得了重大进展 在清醒的行为动物中进行调节，我们的知识中仍然存在关于如何无感觉的显著差距 与行为状态变化相关的内部因素会影响感觉信号。首先，我们目前 对行为状态如何调制视觉信号的理解仍然局限于大脑皮层，重点较少 大脑皮质的输入，比如来自丘脑的输入，这是一个大脑区域，受到强烈的 行为状态的改变。第二，虽然人们普遍认为自发因素，如 跑步、甩动和唤醒的变化可以调节视觉活动，很少有研究将这些因素纳入 帐号。如果不考虑非感官因素，我们就不能完全理解潜在的神经回路 在主动行为中的感觉反应。因此，随着系统神经科学领域走向 要了解清醒行为动物的感觉过程，迫切需要了解多早 感觉处理是由清醒行为状态的变化来调节的。拟议的项目将结合 同时记录非感官内部因素，如唤醒和自发的面部运动 丘脑外侧膝状体背侧核(DLGN)的细胞外记录 主动执行视觉空间检测任务。 通过将非感官变量，如唤醒和运动与任务投入和视觉分离 空间注意，我可以检验我的主要假设，即唤醒、任务投入和空间注意的变化， 对dLGN的活性有明显影响。这一假设将通过三个目标进行检验。首先，在目标1中，我会 确定觉醒水平、面部运动和dLGN中视觉反应特性之间的关系 老鼠被动地观看视觉刺激。在目标2中，我将量化刺激检测在行为学中的准确性 任务影响dLGN的视觉反应属性，同时记录非感觉变量，并使用 神经数据与非感觉因素相结合，在逐个试验的基础上预测行为结果 广义线性模型(GLM)，以了解哪些预测因素对行为结果有显著影响。 在目标3中，我将确定视觉空间注意如何调制dLGN中的视觉反应，同时记录非 感觉变量和认知状态的分离变化与唤醒和运动的变化 对视觉空间注意的回路机制有了更全面的理解。总而言之，这些实验 将详细描述感觉活动和非感觉活动是如何相互补充的 在dlgn水平上是可分离的。这项工作将强调解释非感官的迫切需要 内部变量，以及行为状态变化对早期视觉信号的影响。

PROJECT SUMMARY/ABSTRACT While significant advances have been made over the past decade in understanding how sensory responses are modulated in the awake behaving animal, significant gaps in our knowledge still remain about how non-sensory internal factors related to changes in behavioral state can impact sensory signaling. First, our current understanding of how visual signaling is modulated by behavioral state is still limited to cortex with less emphasis on the inputs to cortex such as those coming from the thalamus, which is a brain region strongly modulated by changes in behavioral state. Second, while it has been widely recognized that spontaneous factors such as running, whisking, and changes in arousal can modulate visual activity, very few studies take these factors into account. Without accounting for non-sensory factors, we cannot fully understand the neural circuitry underlying sensory responses during active behavior. Thus, as the field of systems neuroscience moves towards understanding sensory processing in awake behaving animals, there is a critical need to understand how early sensory processing is modulated by shifts in the waking behavioral state. The proposed project will combine the recording of non-sensory internal factors such as arousal and spontaneous face movements with simultaneous extracellular recordings from the dorsal lateral geniculate nucleus (dLGN) of the thalamus while animals are actively performing a visual spatial detection task. By dissociating non-sensory variables such as arousal and movement from task engagement and visual spatial attention, I can test my main hypothesis that shifts in arousal, task-engagement, and spatial attention, have distinct effects on activity in dLGN. This hypothesis will be tested through three Aims. First, in Aim 1 I will determine the relationship between arousal level, face movement, and visual response properties in dLGN in mice passively viewing visual stimuli. In Aim 2, I will quantify how stimulus detection accuracy in a behavioral task impacts visual response properties in dLGN while simultaneously recording non-sensory variables, and use neural data combined with non-sensory factors to predict behavioral outcome on a trial-by-trial basis with a generalized linear model (GLM) to understand which predictors significantly contribute to behavioral outcome. In Aim 3, I will determine how visual spatial attention modulates visual responses in dLGN while recording non- sensory variables and dissociate changes in cognitive state from changes in arousal and movement to gain a more complete understanding of the circuit mechanisms of visual spatial attention. Together, these experiments will yield a detailed characterization of how sensory activity and non-sensory activity can be both complementary and dissociable at the level of dLGN. This work will underscore both a critical need to account for non-sensory internal variables, and the impact of shifts in behavioral state on early visual signals.