Intrinsic electrical properties shape feature selectivity in a novel retinal ganglion cell

新型视网膜神经节细胞的固有电特性形状特征选择性

• 批准号: 10227920
• 负责人: Sophia Rose Wienbar
• 金额: $ 3.96万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227920
• 关键词: Action Potentials; Afferent Neurons; Biophysical Process; Biophysics; Brain; Cells; Classification; Closure by clamp; Data; Diagnosis; Fire - disasters; Goals; Immunohistochemistry; Individual; Injections; Inner Plexiform Layer; Ion Channel; Knowledge; Light; Light Cell; Measures; Morphology; Mus; Names; Neurons; Output; Pharmacology; Physiology; Population Heterogeneity; Process; Property; Research; Retina; Retinal Diseases; Retinal Ganglion Cells; Role; Sensory; Shapes; Signal Transduction; Synapses; Techniques; Testing; Typology; Visual Fields; Work; cell type; density; detector; differential expression; electrical property; experimental study; neuromechanism; neuronal excitability; novel; relating to nervous system; response; single-cell RNA sequencing; transcriptomics; visual process; voltage clamp

Project Summary Neurons use their intrinsic properties to integrate and perform computations on their synaptic inputs. When considering possible mechanisms of neural computations, two primary components to consider are the network that the neuron belongs to and the intrinsic properties of the neuron itself. My proposed project uses a newly discovered retinal ganglion cell (RGC) type in mouse retina to create a clean experimental separation between network and intrinsic aspects of a sensory computation. I have identified a novel retinal ganglion cell (RGC) type: the “Bursty Suppressed-by-Contrast” (bSbC). The primary functional classification for RGC types is whether the cells are ON, OFF, ON-OFF, or the more rarely described suppressed-by-contrast (SbC). SbC RGCs suppress their firing rate from baseline to both positive and negative contrast steps. I will determine how synaptic inputs and the intrinsic properties of the bSbC support this contrast response profile. I will compare the bSbC to a well-known RGC type called the OFF sustained alpha (OFFsA) because these two cell types, despite their key functional difference, have similar morphology and similar synaptic inputs. My preliminary data suggest that differences in intrinsic properties between these two RGC types are responsible for their different contrast response functions. I will compare the intrinsic properties of the bSbC and the OFFsA using a combination of current clamp and voltage clamp recordings, single cell RNAseq, immunohistochemistry, and pharmacology. This project demonstrates that two distinct cell types in similar synaptic networks can have markedly different outputs due to intrinsic properties. I will able to dissect the contribution of channel typology and density to a specific neuronal computation. This work will deepen our understanding of retinal circuitry and, more generally, it will provide a template for dissecting the relative contribution of intrinsic properties in all neural computation.

项目摘要 神经元利用其固有特性来整合和执行其突触输入的计算。当 考虑到神经计算的可能机制，需要考虑的两个主要组成部分是网络 以及神经元本身的内在属性。我提议的项目使用一种新的 在小鼠视网膜中发现了视网膜神经节细胞（RGC）类型， 感知计算的网络和内在方面。 我已经确定了一种新的视网膜神经节细胞（RGC）类型：“对比度抑制爆发”（bSbC）。的 RGC类型的主要功能分类是细胞是ON、OFF、ON-OFF还是更罕见的 对比度抑制（SbC）。SbC RGC抑制它们的放电率从基线到正和负两者。 负对比步骤。我将确定突触输入和bSbC的内在属性如何支持这一点 对比度响应曲线。 我将比较bSbC和一种著名的RGC类型，称为OFF持续alpha（OFFsA），因为这两种类型 尽管细胞类型的关键功能不同，但它们具有相似的形态和相似的突触输入。我 初步数据表明，这两种RGC类型之间内在特性的差异是导致 不同的对比度响应函数。我将比较bSbC和OFFsA的固有特性 使用电流钳和电压钳记录的组合，单细胞RNAseq，免疫组织化学， 和药理学。 该项目表明，在相似的突触网络中，两种不同的细胞类型可以具有明显不同的 输出由于内在属性。我将能够剖析渠道类型和密度的贡献， 特定的神经元计算。这项工作将加深我们对视网膜回路的理解，更广泛地说， 它将为剖析所有神经计算中内在属性的相对贡献提供一个模板。