Behavior-dependent neuromodulation of retinogeniculate axonal boutons

在小鼠中，有超过30种不同的视网膜神经节细胞类型编码视觉场景， 传输关于运动方向、取向、位置、大小和亮度的信息。这些细胞 类型提供了关于周围环境的丰富细节。然而，在某些大脑状态和 行为，一些信息渠道比其他渠道更重要。例如在 运动或觅食，视觉处理你面前的物体可能比 检测某些视觉线索，例如来自迫近的捕食者的微弱威胁线索。的近期研究 皮层和丘脑已经确定了突触和回路机制， 特定相关视觉刺激和/或抑制不相关信息。在这 陈和Andermann实验室提出了一个假设，即状态依赖 视觉灵敏度的调节开始于视觉通路中的更早的站，在 视网膜神经节细胞末梢，因为它们支配背外侧核（LGN），视觉神经节细胞末梢， 丘脑此外，这种敏感性可以通过5-羟色胺的直接神经调节作用来赋予。 Andermann实验室将对不同视网膜神经元的视网膜轴突终扣的视觉反应进行成像。 神经节细胞类型在安静的清醒和觉醒状态下， LGN中的信号。Chen实验室将进行体外电生理学实验， 5-羟色胺在不同遗传类别的LGN视网膜输入中的突触前调制幅度， 使用视网膜轴突的遗传亚型的双色光遗传学激活， LGN中的轴突终末。如果我们的假设得到证实，这种协同合作 两个实验室之间的合作将建立一个概念上新颖的框架， 调制的早期视觉处理和感知，并提供重要的见解， 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.