How vesicles send information to retinal ganglion cells

囊泡如何向视网膜神经节细胞发送信息

基本信息

批准号：
7494515
负责人：
MICHAEL A FREED
金额：
$ 37.47万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-03-01 至 2010-02-28
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Retinal circuits transfer prodigious amounts of information using graded release of synaptic vesicles. Vesicles are expensive to manufacture, transport, and refill; also their quantal postsynaptic currents discharge ionic batteries that use about one-third of the retina's total energy. Therefore, vesicles must be used judiciously. This implies that upstream of the well-studied spike code, there must be a "vesicle code". Although the mechanics of vesicle release are no longer a complete mystery, the important question of how vesicles encode information has hardly been broached. The information that one vesicle conveys to a ganglion cell is not fixed. Rather, it depends on how many other vesicles are delivering the same message. Release from multiple sites of the same presynaptic neuron and from different neurons with overlapping receptive fields carries redundant messages and thus reduces information per vesicle. Vesicle redundancy, though expensive, is essential. For example it improves signal-to-noise and helps create a receptive field center. Here I propose to apply methods from studies of spike coding to measure information rates for vesicles and thus discover some principles for a vesicle code. Recording under voltage clamp, I will measure bits/vesicle and test the following hypotheses: (1) higher rates of bipolar cell quanta in a ganglion cell should reduce net information per quantum. Evoke similar quantal rates in different ganglion cell types (brisk-sustained and sluggish) and test whether brisk-sustained cells, with less redundancy, have more bits/vesicles. (2) Total information conveyed separately by amacrine and bipolar cell vesicles should exceed that of their combined quantal currents. Isolate quantal currents from amacrine and bipolar cells and determine separate information rates. Record combined current and determine combined information rate. (3) Information is lost between the vesicle code and spike code. Compare information rates for quantal currents vs. spike train. (4) Ganglion cells select from multiple bipolar cell types with distinct pass bands. Determine if different frequency components produce distinct quantal currents. Characterize the pass bands of identified types of bipolar cell. Determine which bipolar cell types contact different ganglion cell types. The proposed studies, by measuring information flow at the level of synaptic currents, will develop explicit rules that connect low-level synaptic mechanisms to higher-level circuit architectures and thus contribute to fundamental understanding of retinal function.

描述（由申请人提供）：视网膜电路使用突触囊泡的分级释放传输大量信息。囊泡的制造，运输和补充价格昂贵；他们的数量突触后电流排放了使用视网膜总能量的三分之一的离子电池。因此，必须明智地使用囊泡。这意味着在经过良好的尖峰代码的上游，必须有一个“囊泡代码”。尽管囊泡释放的力学不再是一个完全的谜团，但几乎没有解释了囊泡如何编码信息的重要问题。一个囊泡传达给神经节细胞的信息没有固定。相反，这取决于其他囊泡传递了相同的消息。从同一突触前神经元的多个位点释放，并从具有重叠接收场的不同神经元中释放出冗余消息，从而减少每个囊泡的信息。囊泡冗余虽然昂贵，但至关重要。例如，它改善了信号到噪声，并有助于创建一个接受场中心。在这里，我建议将峰值编码研究中的方法应用于囊泡的信息速率，从而发现囊泡代码的一些原理。在电压夹下记录，我将测量钻头/囊泡并检验以下假设：（1）神经节细胞中的双极细胞量子的速率更高，应减少每个量子的净信息。在不同的神经节细胞类型（轻快的和缓慢）中引起相似的量化速率，并测试冗余性较小的轻快细胞是否具有更多的位/囊泡。（2）通过两极分裂和双极细胞囊泡分别传达的总信息应超过其合并的量子电流。分离出从积极和双极细胞中分离出数量电流，并确定单独的信息速率。记录当前的组合并确定组合信息率。（3）囊泡代码和尖峰代码之间丢失了信息。比较数量电流与尖峰火车的信息率。（4）神经节细胞从具有独特的通过带的多种双极细胞类型中进行选择。确定不同的频率分量是否产生不同的量电流。表征已鉴定的双极细胞类型的通行带。确定哪些双极细胞类型接触不同的神经节细胞类型。提出的研究通过测量突触电流水平的信息流，将制定明确的规则，这些规则将低级突触机制与高级电路体系结构联系起来，从而有助于对视网膜功能的基本了解。