The vesicle code transmitting visual information

大脑的基本功能是处理信息。在神经元内，这种信息由单个符号的存在或不存在来表示，就像计算机中的0和1一样。这个符号是一种电脉冲，叫做尖峰。但是“尖峰密码”只是故事的一半，因为信息是通过称为神经递质的化学物质脉冲在神经元之间传递的。这种化学密码的基本符号是神经元在突触连接处释放的神经递质包，但与我们对尖峰密码的理解相比，我们对囊泡密码的理解非常有限。人们一直认为，突触通过独立释放单个囊泡来表达信息，释放更多的囊泡表示更大的数量，例如更强的刺激。最近，我们使用先进的光学显微镜来分离来自活斑马鱼视网膜中单个兴奋性突触的信号，因为它们对视觉刺激做出反应，这提供了一个新的图片。视网膜中的一些突触不仅使用两个符号，而是多达十个或十一个，由一个，两个，三个或更多个囊泡作为单一事件释放组成。这个过程被称为多泡释放，是许多大脑区域突触连接的特征，但它在信息处理中的作用尚不清楚。这项提议使用斑马鱼来构建这项工作，并分析在视觉的前三个突触阶段（从视网膜到下游电路）传递信息的囊泡代码。我们的中心假设是，所有的突触在早期视觉是能够编码信息的变化，在这两个突触事件的速度和幅度，但在不同程度上，这取决于突触的结构和神经元传递的信息。视觉信息是如何从光感受器传递的？在视网膜回路的输入端，光感受器将视觉刺激编码为膜电位的分级（“模拟”）变化，这些变化通过专门用于传输第一视觉信号的“带状”突触重新编码。我们将测试这一假设，即感光突触作为一个“时钟”，减少了信号传输的变化性，增加了视觉信号的可靠性。双极细胞中丢失了多少视觉信息？当视觉信号到达视网膜的输出神经元（RGC）时，它已经被转换为数字形式的尖峰。这个过程是视觉处理的基础，通常被认为发生在RGC中，但我们已经证明它可以开始于双极细胞的突触内，双极细胞是连接光感受器和RGC的神经元。BC作为信息瓶颈，也通过“带状”突触传递信号，尽管其结构与光感受器中的结构不同。我们将测试不同的BC根据其功能角色传递不同数量的信息的假设。目标3。鱼的眼睛向鱼的大脑发送了多少信息？视网膜将视觉输入分解成明亮和黑暗的区域，不同大小或方向的物体，以不同的速度和不同的方向移动。视觉输入的这些不同方面通过不同的RGC流到大脑的不同部分。许多RGC向多个目标电路发送信号，但我们不知道它们是否发送相同的消息。我们现在需要了解有多少视觉信息可以通过传统的突触传递，以及它们如何有效地利用突触囊泡。我们将测试这一假设，即不同的RGC在不同程度上使用MVR来向不同的目标传递不同数量的信息。通过关注视觉，这个项目将帮助我们了解大脑中突触最基本的功能-信息传递。

The fundamental function of the brain is to process information. Within neurons this information is represented by the presence or absence of a single symbol, much like zero's and one's in a computer. This symbol is an electrical pulse called a spike. But the "spike code" is only half the story because information is transmitted between neurons by pulses of chemicals called neurotransmitters. The basic symbol for this chemical code is the packet of neurotransmitter released from a neuron at a synaptic connection but, compared to our understanding of the spike code, we have very little understanding of the vesicle code.It has been assumed that synapses represent information by releasing individual vesicles independently, with more being released to signify a larger quantity such as a stronger stimulus. We recently used advanced optical microscopes to isolate the signals from individual excitatory synapses in the retina of live zebrafish as they responded to visual stimuli and this provided a new picture. Some synapses in the retina use not just two symbols, but up to ten or eleven, comprised of one, two, three or more vesicles released as a single event. This process, termed multivesicular release, is a feature of synaptic connections in many brain regions but it's role in information processing is not known. This proposal uses zebrafish to build from this work and analyze the vesicle code transferring information at the first three synaptic stages of vision, from the retina to downstream circuits. Our central hypothesis is that all the synapses in early vision are capable of encoding information as changes in both the rate and amplitude of synaptic events but to varying degrees, depending on the structure of the synapse and the information transmitted by the neuron.We will investigate this hypothesis through three overlapping questions: Aim 1. How is visual information transmitted from the photoreceptors? At the input to the retinal circuit, photoreceptors encode visual stimuli as graded ("analogue") changes in membrane potential and these are recoded through "ribbon" synapses specialized for transmitting the first visual signals. We will test the hypothesis that photoreceptor synapses increase the reliability of the visual signals by acting as a "clock" that reduces the variability of the signal transmitted.Aim 2. How much visual information is lost in bipolar cells? By the time the visual signal reaches the output neurons of the retina (RGCs), it has been converted into the digital form of spikes. This process is fundamental to visual processing and is often assumed to occur in RGCs, but we have shown that it can begin within the synapse of bipolar cells, the neurons that connect photoreceptors to RGCs. BCs act as an information bottleneck and also transmit signals through "ribbon" synapses, although with structures distinct from those in photoreceptors. We will test the hypothesis that different BCs transmit different amount of information depending on their functional role. Aim 3. How much information does the fish's eye send to the fish's brain? The retina decompose the visual input into areas of bright and dark, objects of different size or orientation, moving at different speeds and in different directions. These different aspects of the visual input are streamed to different parts of the brain through different RGCs. Many RGCs send signals to more than one target circuit but we do not know if they send the same message . We now need to understand how much visual information can be transmitted through conventional synapses and how efficiently they use synaptic vesicles. We will test the hypothesis that individual RGCs employ MVR to differing degrees to transmit different amounts of information to different targets.By focusing on vision, this project will help us understand the most fundamental function of synapses in the brain - the transfer of information.