Synapses as Independent Computational Units in the Excitatory Pathways of the Retina

项目总结/摘要 确定神经元回路的计算单位对于理解回路的功能是必不可少的 作为一个整体。在许多回路中，亚细胞区室化使得突触前侧的突触终扣， 和突触后侧的树突独立运作。在感觉系统中， 发散允许使用有限数量的 神经元视网膜是研究电路模体突触机制的有利模型系统，如 功能分歧，因为我们先进的知识，细胞类型和电路结构在视网膜 让我们能够针对视觉刺激提出关于连接性和功能的精确问题。 在小鼠视网膜中，信号从两种锥细胞类型分叉到约15种双极细胞（BC）类型，然后分叉到> 40种视网膜细胞类型。 神经节细胞（RGC）类型在输出水平。功能分化的机制在 视网膜中的第一个突触，但对第二个突触的机制知之甚少，从BCs到 RGC。我的工作将通过建立一个模型系统来填补这一空白，在这个模型系统中，单个BC类型分叉， 两种不同类型的研资局提供不同功能的输入数据。这个项目的核心假设是， 来自同一BC的突触可以作为独立的计算单元，中继不同的模式， 释放谷氨酸给突触后的伴侣 在目标1中，我们将获得生理学证据，证明这两种RGC类型共享来自不同突触的输入 相同的BC。在目标2中，我们将用电子显微镜测量突触的超微结构， 确定突触后RGC身份对BC突触结构的作用。在目标3中，我们 演示BC终端内的功能区室化，首先使用电紧张建模 方法，然后与谷氨酸释放的实验测量。 这个项目的成功完成将解决单个BC是否可以传输的问题 功能上不同的谷氨酸信号来自不同的突触。确认功能分歧， BC突触的水平将改变我们对视网膜回路计算结构的看法。而不是 考虑到双极细胞作为兴奋的计算单位，我们将证明双极细胞的输出 突触可以执行独立的计算。这种模式的变化将对以下方面产生重要影响： 模型的视网膜电路，它将开辟新的研究领域的分子决定因素的亚细胞 发育中的接线特异性。

Project Summary/Abstract Determining the computational units of a neuronal circuit is essential in understanding the function of the circuit as a whole. In many circuits, subcellular compartmentalization allows synaptic boutons on the presynaptic side, and dendrites, on the post-synaptic side, to functional independently. In sensory systems, functional divergence allows enabled the representation of many features of a stimulus using a limited number of neurons. The retina is an advantageous model system for studying synaptic mechanism of circuit motifs, like functional divergence, because our advanced knowledge of cell types and circuit architecture in the retina allows us to ask precise questions about connectivity and function in response to visual stimuli. In the mouse retina, signals diverge from two cone types to ~15 bipolar cell (BC) types, and then to > 40 retinal ganglion cell (RGC) types at the output level. Mechanisms for functional divergence are well established at the first synapse in the retina, but much less is known about mechanisms at the second synapse, from BCs to RGCs. My work will fill this gap by establishing a model system in which a single BC type diverges to provide functionally distinct input to two different RGC types. The core hypothesis of this project is that different synapses from the same BC can act as independent computational units, relaying different patterns of glutamate release to their postsynaptic partners. In Aim 1, we will obtain physiological evidence that these two RGC types share input from different synapses on the same BCs. In Aim 2, we will measure the ultrastructure of the synapses with electron microscopy to determine the role of postsynaptic RGC identity on the structure of the BC synapses. In Aim 3, we will demonstrate functional compartmentalization within the BC terminal, first with an electrotonic modeling approach, and then with experimental measurements of glutamate release. The successful completion of this project will resolve the question of whether individual BCs can transmit functionally distinct glutamate signals from different synapses. Confirmation of functional divergence at the level of BC synapses will alter our picture of the computational structure of retinal circuits. Instead of considering bipolar cells as the computational units of excitation, we will instead show that bipolar cell output synapses can perform independent computations. This paradigm change will have important consequences for models of retinal circuits, and it will open up new areas of study into the molecular determinants of subcellular wiring specificity in development.