Reverse-engineering Drosophila's retinal networks

视觉是许多生物最重要的感觉。即使在最昏暗的栖息地，动物的眼睛也有功能，这使它们能够从环境中提取有用的光学信息，并对变化的事件和条件做出迅速而适当的反应。解剖结构、分子信号级联以及生物体视觉系统的最终性能，以速度、灵敏度、动态范围和稳健性来衡量，已经通过光刺激的内容以及其他环境因素来调整以适应其生活方式。无脊椎动物的视觉是广泛研究的主题，它导致了适用于所有感官的重要基本原理的发现。果蝇视觉系统是研究早期神经加工机制的理想模型，具有数十年遗传、解剖、生理和行为研究的丰富详细知识。果蝇第一视觉突触层的超微结构已经从电子显微切片中得到了完整的描述。大量的分子遗传学方法结合生化分析和细胞内记录技术已经汇聚在果蝇的视觉系统上，提供了前所未有的实验可追溯性。这些方法使识别其信号级联的要素成为可能，并为相关的调节机制提供了独特的见解。苍蝇光感受器的信号处理能力是惊人的，在许多方面优于人类工程图像传感器。它们非常敏感，能够对单光子事件做出反应。嵌入在噪声中的弱输入信号可以选择性地放大和过滤，以提供有效和可靠的生理相关刺激感测。光感受器的一个令人着迷的功能属性，尚未在工程传感设备中复制，是它们的光适应能力，即根据过去和正在进行的光事件调整放大增益，使用多层正反馈和负反馈控制。这使得它们可以在很宽的环境范围内工作。它们可以在适应黑暗的条件下可靠地响应单光子的吸收，但也可以调整增益以在明亮的日光条件下工作。该项目旨在利用从控制和系统工程中借鉴的数学工具和技术，开发一个详细的早期视觉系统数学模型，使我们能够了解不同分子成分在将光转换为电信号中的作用，以及苍蝇的光感受器必须遵守的适应规则，以便在黑暗和充分的光照下可靠地工作。

Vision is the most important sense of many living organisms. Even in the dimmest habitats animals have functional eyes, which allow them to extract useful optical information from the environment and to respond rapidly and appropriately to changing events and conditions. The anatomical structure, molecular signalling cascades and ultimately the performance of an organism's visual system, measured in terms of speed, sensitivity, dynamic range and robustness, has been tuned to suit its lifestyle by the content of the photic stimuli as well as other environmental factors. Vision of invertebrate species was the subject of extensive research which led to the discovery of important fundamental principles that apply to all senses. Drosophila visual system is an ideal model to investigate the mechanisms underlying early neural processing with a wealth of detailed knowledge from tens of years of genetic, anatomical, physiological and behavioural studies. The ultrastructure of the first visual synaptic layer in Drosophila has been fully described from electron-micrograph sections. A vast array of molecular genetic methods combined with biochemical analysis and intracellular recording techniques have converged on Drosophila's visual system providing unprecedented experimental tractability. These methodologies have made possible the identification of elements of its signalling cascades and offered unique insight into the associated regulatory mechanisms. The signal-processing capability of fly photoreceptors is prodigious, outperforming human engineered image sensors in many respects. They are exquisitely sensitive, being able to respond to single photon events. Weak input signals embedded in noise can be selectively amplified and filtered to provide efficient and reliable sensing of physiologically relevant stimuli. A fascinating functional attribute of photoreceptors, that is yet to be replicated in an engineering sensing device, is their ability to light adapt, i.e. adjust the amplification gain, according to both past and on-going light events, using many layers of positive- and negative-feedback control. This allows them to operate over a wide environmental range. They can reliably respond to the absorption of single photons under dark-adapted conditions, but can also adjust the gain to operate in bright daylight conditions. This project aims to develop, using mathematical tools and techniques borrowed from control and systems engineering, a detailed mathematical model the early vision system that will allow us to understand the role of different molecular components that are instrumental in converting light into electrical signals and the adaptation rules that fly photoreceptors must obey in order to operate reliably in dark as well as in full shinshine.