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

项目摘要/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，亚细胞分区允许突触前侧的突触突触， 而突触后侧的树突可以独立发挥作用。在感觉系统中，功能 发散性允许使用有限数量的 神经元。视网膜是研究回路基元突触机制的有利模型系统，如 功能分化，因为我们对视网膜细胞类型和电路结构的高级知识 使我们能够对视觉刺激提出关于连通性和功能的精确问题。 在小鼠视网膜中，信号从两种锥体类型到~15个双极细胞(BC)类型，然后到&gt；40视网膜 输出水平的神经节细胞(RGC)类型。功能分化的机制在 第一个突触在视网膜，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，在该模型系统中，单个BC类型将提供 两种不同类型的研资局在功能上不同的输入。这个项目的核心假设是不同的 来自同一BC的突触可以作为独立的计算单位，传递不同的模式 谷氨酸释放给它们突触后的伙伴。 在目标1中，我们将获得这两种类型的RGC共享来自不同突触的输入的生理学证据 在同一个BCS上。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在BC突触结构中的作用。在《目标3》中，我们将 演示BC终端内的功能分区，首先使用电子张力建模 方法，然后用实验测量谷氨酸的释放。 该项目的顺利完成将解决单个BCS能否传输的问题 来自不同突触的功能不同的谷氨酸信号。功能分化的确认 BC突触的水平将改变我们对视网膜回路计算结构的认识。而不是 考虑双极电池作为激发的计算单位，我们将改为显示双极电池的输出 突触可以执行独立的计算。这一范式变化将对以下方面产生重要影响 视网膜回路模型，并将开辟研究亚细胞分子决定因素的新领域 发育过程中的连线专一性。

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.