Single-cell computation in auditory brainstem and its impact on cortical coding and behavior

听觉脑干中的单细胞计算及其对皮质编码和行为的影响

• 批准号: 10455326
• 负责人: Nace L Golding
• 金额: $ 10.06万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10455326
• 关键词: Anatomy; Animals; Auditory; Auditory Perception; Auditory area; Auditory system; Axon; Behavior; Behavioral; Binding; Biological Models; Biophysics; Brain; Brain Stem; Brain imaging; Cell physiology; Cells; Cochlea; Cochlear nucleus; Code; Complex; Computer Models; Computing Methodologies; Data; Decision Making; Dendrites; Detection; Disease; Ear; Electron Microscopy; Electrophysiology (science); Elements; Experimental Models; Frequencies; Gene Expression Profiling; Goals; Head; Hearing; Image; In Vitro; Individual; Inferior Colliculus; Learning; Link; Methods; Midbrain structure; Modeling; Molecular; Molecular Analysis; Morphology; Mouse Strains; Mus; Neurons; Octopus; Output; Pattern; Perception; Performance; Physiological; Physiology; Play; Population; Positioning Attribute; Process; Property; Psychometrics; Resolution; Role; Sensory; Shapes; Speech; Stimulus; Stream; Study models; Synapses; System; Testing; Thalamic structure; Time; Training; Translating; Travel; Whole-Cell Recordings; Work; auditory pathway; auditory thalamus; awake; base; biophysical analysis; brain cell; cell type; confocal imaging; experimental study; in vivo; insight; millisecond; multidisciplinary; nervous system disorder; neuronal circuitry; novel strategies; optogenetics; parallel processing; patch sequencing; predictive modeling; reconstruction; response; sensory input; sensory mechanism; sensory system; sound; spatiotemporal; spiral ganglion; success; tool; transcriptome sequencing; two-photon; voltage

Project Abstract Understanding how neuronal computations build up a perception of the external world is fundamental to our understanding of how the brain works. This is particularly relevant to sensory systems, where heterogenous inputs representing distinct sensory features must be re-assembled to generate a perception. How individual neurons in early stages of sensory circuits process parallel inputs, and how these circuit elements later contribute to cortical computations that bind the inputs together is completely unknown. Studies have demonstrated that the timing, position and strength of a given input along the dendrite of a given neuron is a critical strategy used by the brain to encode sensory features. However, how such dendritic integrations of inputs in single neurons contribute to an animal's overall perception is not understood. To re-assemble diverse features from the same initial stimulus, the brain needs to determine which features occurred at the same time. Currently, little is known about how or where this timing information might be encoded. The auditory system offers an ideal system to tackle this question based on its tractability to interdisciplinary methods and its known ability to encode even miniscule differences in timing. Specifically, we will take advantage of a unique cell type in the auditory cochlear nucleus, called octopus cells, as a model to investigate the question of how small cell classes contribute to behavioral and perceptual circuits. Octopus cells are prominent in all mammalian species and are well known to encode temporal inputs with submillisecond precision through integration of primary sensory inputs along their large and extensive dendrites. We propose to carry out a multi- lab, integrated analysis of the molecular and biophysical properties of octopus cells and to track how these single cell computations are transformed along the auditory pathway to contribute to an animal's final auditory percept and hence behavior. Using the mouse as a model system, we will apply new sequencing methods together with high resolution brain imaging and single cell reconstructions to create a comprehensive wiring diagram of octopus cells and their auditory inputs. By generating mouse strains for selective access to octopus cells, we will be ideally positioned to investigate the in vitro and in vivo physiology of octopus cells and therefore bridge experimental and computational models for how timing information is encoded at the single cell level. Lastly, we will study how timing information propagates to higher auditory centers by recording from large populations of neurons in the midbrain, thalamus, and cortex and then assessing the functional relevance of temporal coding for auditory behavior. By leveraging molecular, biophysical, electrophysiological, behavioral, and computational approaches toward the study of this model cell type, these studies will allow us to extract general principles of single cell computations and their effects on systems-level circuit function, with broad implications for understanding how parallel streams of information are integrated to generate sensory perception.

项目摘要 了解神经元计算如何建立对外部世界的感知至关重要 了解大脑的工作原理。这与感觉系统特别相关 必须重新组装代表不同感觉特征的输入以产生感知。多么个人 在感觉电路的早期阶段的神经元处理平行输入，这些电路元素如何贡献 对于将输入结合在一起的皮质计算是完全未知的。研究表明 给定神经元的树突的给定输入的时间，位置和强度是使用的关键策略 通过大脑编码感官特征。但是，单个神经元中输入的这种树突状积分如何 尚不清楚为动物的整体看法做出贡献。 要重新组装出相同初始刺激的多种功能，大脑需要确定哪些功能 同时发生。当前，对于如何或何处可以编码此时间或何处。 听觉系统提供了一个理想的系统，可以根据其跨学科的障碍来解决此问题 方法及其已知的编码时间差异的能力。具体来说，我们将利用 听觉耳蜗核中独特的细胞类型，称为章鱼细胞，作为研究问题的模型 小细胞类别如何促进行为和感知电路。章鱼细胞在所有人中很突出 通过 将主要感觉输入沿其大而广泛的树突的整合。我们建议执行多个 实验室，对章鱼细胞的分子和生物物理特性的综合分析，并跟踪这些单个单一的 细胞计算沿听觉途径进行转换，以促进动物的最终听觉感知 因此行为。使用鼠标作为模型系统，我们将与 高分辨率的大脑成像和单细胞重建，以创建全面的接线图 章鱼细胞及其听觉输入。通过生成小鼠应变以选择性访问章鱼细胞，我们将 理想的位置可以研究章鱼细胞的体外和体内生理，因此桥接 定时信息如何在单个单元格级别编码的实验和计算模型。最后，我们 将研究计时信息如何通过记录大量人群来传播更高的听觉中心 中脑，丘脑和皮层中的神经元，然后评估时间编码的功能相关性 用于听觉行为。通过利用分子，生物物理，电生理，行为和计算 研究该模型细胞类型的方法，这些研究将使我们能够提取 单单元计算及其对系统级电路函数的影响，对 了解如何集成信息流以产生感觉知觉。