Behavior-dependent neuromodulation of retinogeniculate axonal boutons

在老鼠身上，有30多种不同类型的视网膜神经节细胞编码视觉场景， 传输有关运动方向、方向、位置、大小和亮度的信息。这些细胞 类型提供了有关周围环境的丰富细节。然而，在某些大脑状态和 在行为上，一些信息渠道比其他渠道更重要。例如，在 运动或觅食，对你面前物体的视觉处理可能比 检测某些视觉线索，例如来自隐约可见的捕食者的微弱威胁线索。最近的研究 皮质和丘脑已经确定了突触和回路机制，这些机制提高了对 具体相关的视觉刺激和/或抑制不相关的信息取决于大脑状态。在这 建议，陈和安德曼实验室建议检验一个假设，即依赖于国家 视觉敏感度的调节开始于视觉通路中更早的位置，在 视网膜神经节细胞终末支配视觉背外侧核(LGN) 丘脑。此外，这种敏感性可能是通过5-羟色胺的直接神经调节作用来实现的。 安德曼实验室将对不同视网膜轴突的视觉反应进行成像 操纵5-羟色胺能神经时安静清醒和觉醒状态下的神经节细胞类型 LGN中的信令。陈实验室将进行体外电生理学实验，以评估 5-羟色胺对LGN不同遗传类型视网膜输入突触前调制的幅度， 利用双色光遗传激活视网膜轴突的遗传亚型，并结合刺激 LGN内5-羟色胺能轴突终末。如果我们的假设得到证实，这种协同合作 这两个实验室之间将建立一个概念上的新框架来理解行为 对早期视觉加工和知觉的调节，并对精神障碍提供了重要的见解 认知和视觉感知。

In mice, there are more than 30 different retinal ganglion cell types that encode the visual scene, transmitting information about motion direction, orientation, location, size and luminance. These cell types provide rich detail about the surrounding environment. However, during certain brain states and behaviors, some channels of information are more important than others. For example, during locomotion or foraging, visual processing of objects in front of you may be more important than detection of certain visual cues, such as weak threat cues from looming predators. Recent studies in the cortex and thalamus have identified synaptic and circuit mechanisms that heighten sensitivity to specific relevant visual stimuli and/or suppress irrelevant information depending on brain state. In this proposal, the Chen and Andermann laboratories propose to test a hypothesis that state-dependent modulation of visual sensitivity begins at a much earlier station in the visual pathway, at the level of the retinal ganglion cell terminals as they innervate the dorsal lateral nucleus (LGN), the visual thalamus. Further, this sensitivity may be conferred by direct neuromodulatory actions of serotonin. The Andermann lab will image visual responses from retinal axonal boutons of different retinal ganglion cell types across states of quiet waking and arousal while manipulating serotonergic signaling in LGN. The Chen lab will perform in vitro electrophysiology experiments to assess the magnitude of presynaptic modulation by serotonin in distinct genetic classes of retinal inputs to LGN, using two-color optogenetic activation of genetic subtypes of retinal axons, together with stimulation of serotonergic axon terminals in LGN. If our hypotheses are confirmed, this synergistic collaboration between the two labs will establish a conceptually novel framework for understanding behavioral modulation of early visual processing and perception, and provide important insights into disorders of cognition and visual perception.