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

• 批准号: 7887307
• 负责人: MICHAEL A FREED
• 金额: $ 39.92万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7887307
• 关键词: Architecture; Brain; Calcium; Cells; Chemical Synapse; Code; Excitatory Synapse; Gap Junctions; Light Adaptations; Lighting; Measurable; Measurement; Measures; Membrane; Nervous system structure; Neurons; Noise; Nose; Pathway interactions; Pattern; Photoreceptors; Prosthesis; Retina; Retinal; Retinal Cone; Retinal Diseases; Retinal Ganglion Cells; Signal Transduction; Source; Synapses; Testing; Vesicle; Vision; cell type; design; ganglion cell; horizontal cell; improved; information processing; presynaptic; public health relevance; quantum; relating to nervous system; retinal rods; visual stimulus; voltage

DESCRIPTION (provided by applicant): Chemical synapses transmit information from one neuron to another throughout the brain. This is accomplished by probabilistic release of transmitter quanta that add noise to the transmitted information. If synapses in a sequential pathway add noise, then noise from one synapse might be transmitted across the next, and synaptic noise will be promulgated throughout the nervous system. Consequently, the brain should be designed to limit the amount of trans-synaptic noise. In the retina, we are beginning to understand how neural noise influences circuit design. Noise causes a measurable reduction in the detectability and discriminability of visual stimuli. To reduce the impact of noise, retinal circuitry is characterized by a pattern of divergence and convergence that sends signal through multiple neurons and synapses. Gap junctions between horizontal cells improve signal-to-nose ratio. Thresholding at the rod ? rod bipolar synapse rejects noise generated in rods. Despite the importance of noise to the function and design of the mammalian retina and brain, the amount of noise that a synapse adds to transmitted information has not been measured; few measurements have been made of the amount of noise passed from one synapse through the next. Synapses are rectifying due to the exponential relationship between membrane voltage and the calcium influx that drives transmitter release. Rectification at the bipolar ? ganglion cell synapse partitions positive and negative contrasts between On and Off pathways, but how this changes with illumination is not known. On and Off signals are recombined in the Off alpha ganglion cell where they may implement a synergistic push-pull circuit. This circuit could improve the overall coding of information, but this has not been directly tested by estimating information rate. Here we propose to investigate the how synapses contribute to retinal information processing by recording EPSCs from a defined subset of retinal ganglion cell types. We will estimate the amount of noise that bipolar synapses on the ganglion cell contribute to these currents. Our preliminary evidence suggests that once this synaptic noise is removed, the remaining noise in the EPSC is from the presynaptic circuit, possibly from quantal release from cone terminals onto bipolar cells. Preliminary evidence suggests that amacrine circuitry, and the partitioning of information into On and Off-pathway are retinal designs that reduce noise. To test these ideas we propose the following specific aims. The proposed studies, by measuring information flow through synapses, will develop explicit rules that connect low-level synaptic mechanisms to higher-level circuit architectures and thus contribute to fundamental understanding of retinal function. By examining how different types of ganglion cell integrate their synaptic input, these studies will contribute to an understanding of how parallel channels are set up by retinal circuits. The proposed studies are relevant to retinal diseases that degenerate photoreceptors but spare ganglion cells: a prosthetic device that stimulates the remaining neurons might restore sight to its original quality, but would need to match the original information rate. Thus providing the right amount and kind of information to each neuron will be critical to prosthetic design. PUBLIC HEALTH RELEVANCE: The proposed studies, by measuring information flow through synapses, will develop explicit rules that connect low-level synaptic mechanisms to higher-level circuit architectures and thus contribute to fundamental understanding of retinal function. The proposed studies are relevant to retinal diseases that degenerate photoreceptors but spare ganglion cells. A prosthetic device that stimulates the remaining neurons might restore sight to its original quality, but would need to match the original information rate. Thus providing the right amount and kind of information to each neuron will be critical to prosthetic design.

描述（由申请人提供）：化学突触将信息从一个神经元传输到整个大脑的另一个神经元。这是通过发射器量子的概率释放来实现的，该量子量子会为发送信息添加噪声。如果在顺序途径中的突触增加噪声，则可能会在下一个突触中传播一个突触的噪声，并将在整个神经系统中颁布突触噪声。因此，应设计大脑以限制跨突触噪声的量。在视网膜中，我们开始了解神经噪声如何影响电路设计。噪声会导致视觉刺激的可检测性和可区分性的可测量降低。为了减少噪声的影响，视网膜电路的特征是发散和收敛的模式，该模式通过多个神经元和突触发送信号。水平细胞之间的间隙连接可以提高信噪比。杆上的阈值？杆双极突触拒绝杆中产生的噪声。尽管噪声对哺乳动物视网膜和大脑的功能和设计很重要，但突触增加的噪声量尚未得到测量。几乎没有测量从一个突触到下一个突触传递的噪声量。由于膜电压与钙涌入的钙涌入，突触正在纠正，从而驱动发射器释放。双极性的纠正？神经节细胞突触分区分区和途径之间的阳性对比和负面对比，但是尚不清楚这如何随照明而变化。在OFF Alpha神经节电池中重新组合了On和Off信号，它们可能会实现协同的推动电路。该电路可以改善信息的整体编码，但这不是通过估计信息率直接测试的。在这里，我们建议研究突触如何通过从视网膜神经节细胞类型的定义子集记录EPSC来促进视网膜信息处理。我们将估计神经节细胞上双极突触有助于这些电流的噪声量。我们的初步证据表明，一旦去除了这种突触噪声，EPSC中的剩余噪声可能来自突触前回路，这可能是从锥端从锥端释放到双极细胞的。初步证据表明，无长束电路以及信息在校外和校外的分区是减少噪声的视网膜设计。为了测试这些想法，我们提出以下特定目标。提出的研究通过测量通过突触的信息流来制定明确的规则，将低级突触机制与高级电路架构联系起来，从而有助于对视网膜功能的基本理解。通过检查不同类型的神经节细胞如何整合其突触输入，这些研究将有助于理解视网膜电路如何设置平行通道。拟议的研究与视网膜疾病疾病有关，但备用神经节细胞的视网膜疾病：一种刺激其余神经元的假体装置可能会恢复其原始质量，但需要匹配原始信息速率。因此，为每个神经元提供适量的信息和类型的信息对于假肢设计至关重要。 公共卫生相关性：拟议的研究通过测量通过突触的信息流来制定明确的规则，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。拟议的研究与视网膜疾病有关，该视网膜疾病将光感受器解脱但备用神经节细胞。刺激其余神经元的假体装置可能会将视线恢复到其原始质量，但需要匹配原始信息速率。因此，为每个神经元提供适量的信息和类型的信息对于假肢设计至关重要。