CRCNS: Biophysical properties of parallel neural circuits serving night vision

该项目的主要目标是将实验和计算方法相结合，以详细了解单个视网膜神经元和突触的生物物理性质如何影响夜视期间视觉信息的并行处理。这个项目是两位神经生物学家和两位应用数学家合作完成的。我们将从实验上描述哺乳动物视网膜的神经回路，并通过计算建立模型，以辅助夜间(暗视眼)视觉。基本电路已经被很好地描述了：被杆状感光器吸收的光子产生神经信号，这些信号通过一系列中间神经元分布到多种类型的视网膜神经节细胞(GC)，即视网膜的输出细胞。这些中间神经元分别发出信号 其他的则通过化学和电子突触。每种GC类型都有独特的光反应，这被认为反映了其独特的突触前回路的特性。这种电路使每种GC类型能够编码视觉场景的一个独特特征，从而促进最终指导行为的高级大脑区域的进一步抽象。通过对每个组件进行表征和仔细建模，通过将组件组装成一个全面的模型，并通过实验验证和改进整个模型，我们将确定并行视网膜微电路的生物物理属性如何产生不同的GC输出。与公共健康的关系：许多视网膜疾病导致感光器(视杆细胞和视锥细胞)死亡，这是 剥夺GC的正常输入。最近，光遗传学方法已经发展起来，最终目的是通过使视网膜神经元直接对光做出反应，在缺乏光感受器功能的情况下恢复视力。在这里，我们希望识别可能被赋予光敏性的关键神经元，以允许恢复在广泛的动态范围内编码视觉世界最相关的特征的能力。 这个项目的目的是解决国家眼科和视觉研究计划中视网膜疾病计划的两个明确目标：1)增加对光感受器后适应的理解(即在神经回路中获得控制)和2)增加对神经网络内视网膜细胞如何相互作用的理解 可解释为视觉图像的信号。

The main goal of this project is to combine experimental and computational approaches to develop a detailed understanding of how the biophysical properties of individual retinal neurons and synapses shape the parallel processing of visual information during night vision. This project is a collaboration between two neurobiologists and two applied mathematicians. We will characterize experimentally and model computationally the neural circuitry of the mammalian retina that subserves night (scotopic) vision. The basic circuitry is well-described: photons absorbed by rod photoreceptors generate neural signals that are distributed to multiple types of retinal ganglion cells (GCs), the output cells of the retina, via a series of interneurons. These interneurons signal each other via chemical and electrical synapses. Each GC type has a unique light response, which is presumed to reflect the properties of its unique presynaptic circuitry. This circuitry enables each GC type to encode a unique feature of the visual scene, thereby facilitating further abstractions by higher brain areas that ultimately guide behavior. By characterizing and carefully modeling each component, by assembling the components into a comprehensive model, and by validating and refining the overall model experimentally, we will determine how diverse GC outputs emerge from the biophysical properties of parallel retinal microcircuits.Relevance to public health: Many retinal pathologies cause photoreceptor (rod and cone) death, which deprives GCs of their normal inputs. Recently, optogenetic approaches have been developed with the ultimate goal of restoring vision in the absence of phoptoreceptor function by making retinal neurons directly responsive to light. Here, we hope to identify key neurons to which photosensitivity may be endowed to permit the restoration of the ability to encode over a wide dynamic range the most relevant features of the visual world. The aims of this project address two explicit goals of the Retinal Diseases Program in the National Plan for Eye and Vision Research: 1) Increasing understanding of post-photoreceptor adaptation (i.e., gain control in neural circuits) and 2) Increasing understanding of how retinal cellular interactions within neural networks generate signals that are interpretable as visual images.