The influence of serotonergic signaling on visual and visuomotor cortical processing

视觉感知及其与运动过程的耦合对于精确的运动行为通常是重要的。知觉和运动动作会在某些情绪状态下受到影响，例如动机、愤怒、恐惧或注意力。5-羟色胺被认为是参与情绪调节的主要递质，特别是作用于G蛋白偶联受体(GPCRs)。已知5-羟色胺能投射支配早期的初级感觉和运动皮质区域。然而，5-羟色胺对视觉和运动皮质活动动力学的影响尚不清楚。此外，视觉区域与皮质运动输出活动密切相关，但这些广泛的区域间相互作用目前还知之甚少。在这项授权中，我们将研究5-羟色胺能递质释放和细胞内信号对视觉和视觉运动皮质处理的影响，并确定涉及哪些5-羟色胺能信号通路。我们将进一步测试5-羟色胺能输入在多大程度上调节局部区域内处理与区域间相互作用的调节。因此，我们将应用光遗传学工具来控制麻醉以及清醒和行为(这里是头部固定)小鼠的5-羟色胺释放和下游信号。此外，我们将在被操纵的大脑网络的脑片中进行单细胞记录，以完成不同水平的网络复杂性的研究。为了捕捉多个大脑区域内和跨多个脑区的网络活动模式，我们将使用电压和钙敏感的荧光传感器进行广域光学成像，这允许以所需的高空间和时间分辨率记录群体活动。我们将在精确控制5-羟色胺能信号的背景下，使用我们的工具来监测视觉任务期间的皮质活动。使用视觉引导的运动活动，即结合视觉流动场输入的简单行走任务，我们将测试5-羟色胺如何调节运动行为，以及这些过程如何在视觉和运动皮质网络活动模式中编码。这些实验将有助于更好地理解5-羟色胺影响下的视觉加工的调制及其对运动调节的重要性。为了进行这些要求苛刻的实验，我们愿意在应用项目中联合我们在光遗传学和活体动物记录方面的专业知识。

Visual perception and its coupling to motor processes are often important for precise motor behavior. Perception and motor action can be influenced during certain emotional states, such as motivation, anger, fear, or attention. Serotonin has been identified as a main transmitter involved in emotional modulation and acts in particular on G protein coupled receptors (GPCRs). Serotonergic projections are known to innervate early primary sensory and motor cortical areas. However, the effects of serotonin on activity dynamics in visual and motor cortex are unknown. Furthermore, visual areas closely interact with cortical motor output activities but these widespread inter-areal interactions are currently poorly understood. In this grant we will investigate the influence of serotonergic transmitter release and intracellular signaling on visual and visuomotor cortical processing and we will determine which serotonergic signaling pathways are involved. We will further test in how far serotonergic input modulates local intra-areal processing vs. modulation of inter-areal interactions. We will therefore apply optogenetic tools for the control of serotonin release and the down-stream signals in anaesthetized as well as awake and behaving (here head-fixed) mice. Additionally, we will perform single-cell recordings in brain slices of the manipulated brain networks to accomplish our investigations at different levels of network complexity. To capture the network activity patterns within and across multiple brain areas we will exploit wide-field optical imaging using voltage- and Ca2+-sensitive fluorescent sensors, which allows recording of population activity at the required high spatial and temporal resolutions. We will use our tools to monitor cortical activity during visual tasks in the context of precise control of serotonergic signals. Using visually-guided motor activity, i.e. a simple walking task combined with visual flow-field input, we will test how serotonin modulates motor behavior and how such processes are encoded in visual and motor cortical network activity patterns. The experiments shall lead to a better understanding of the modulation of visual processing under influence of serotonin and its importance for movement adjustment. In order to perform these demanding experiments we would like to jointly combine our expertise in optogenetics and in in vivo animal recordings in the applied project.