The influence of serotonergic signaling on visual and visuomotor cortical processing

血清素信号对视觉和视觉运动皮层处理的影响

• 批准号: 372419977
• 负责人: Professor Dr. Stefan Herlitze
• 金额: --
• 依托单位: Institut für Neuroinformatik (INI)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/372419977?language=en
• 关键词: influence; serotonergic; signaling; visual; visuomotor

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.

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。感知和运动动作可以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-羟色胺已被确定为参与情绪调节的主要递质，并且特别作用于G蛋白偶联受体（GPCRs）。已知5-羟色胺能投射支配早期初级感觉和运动皮质区。然而，5-羟色胺对视觉和运动皮层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知之甚少。在这项研究中，我们将研究多巴胺能递质释放和细胞内信号传导对视觉和视皮层处理的影响，并确定哪些多巴胺能信号通路参与其中。我们将进一步测试，在多大程度上的负能输入调制局部区域内处理与调制区域间的相互作用。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（这里头部固定）小鼠中的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大脑切片中进行单细胞记录，以完成我们在不同网络复杂程度上的研究。为了捕获多个大脑区域内和跨多个大脑区域的网络活动模式，我们将利用宽视场光学成像，使用电压和Ca 2+敏感的荧光传感器，这允许以所需的高空间和时间分辨率记录群体活动。我们将使用我们的工具来监测皮质活动在视觉任务的背景下，精确控制神经元能信号。使用视觉引导的运动活动，即结合视觉流场输入的简单步行任务，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编码在视觉和运动皮层网络活动模式中。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调制及其对运动调节的重要性。为了完成这些高要求的实验，我们希望在应用项目中共同联合收割机结合我们在光遗传学和体内动物记录方面的专业知识。