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: 10011563
• 负责人: Sophia Rose Wienbar
• 金额: $ 4.55万
• 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 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011563
• 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.

项目概要 神经元利用其内在特性来整合其突触输入并执行计算。 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 神经元所属的属性以及神经元本身的内在属性使用了新的。 在小鼠视网膜中发现了视网膜神经节细胞 (RGC) 类型，从而在实验中将 网络和感知计算的内在方面。 我发现了一种新的视网膜神经节细胞 (RGC) 类型：“对比突发抑制”(bSbC)。 RGC 类型的主要功能分类是细胞是否处于开启、关闭、开启-关闭或更罕见的状态 描述了对比抑制 (SbC) RGC 将其放电率从基线抑制为正和正。 我将确定突触输入和 bSbC 的内在特性如何支持这一点。 对比反应曲线。 我将把 bSbC 与一种称为 OFF 持续 alpha (OFFsA) 的著名 RGC 类型进行比较，因为这两种 细胞类型尽管有关键的功能差异，但具有相似的形态和相似的突触输入。 初步数据表明这两种 RGC 类型之间内在特性的差异是造成这种情况的原因 对于它们不同的对比响应函数，我将比较 bSbC 和 OFFsA 的内在特性。 使用电流钳和电压钳记录、单细胞 RNAseq、免疫组织化学的组合， 和药理学。 该项目表明，相似突触网络中的两种不同细胞类型可能具有显着不同的特征 由于内在属性的输出，我将能够剖析通道类型和密度对 这项工作将加深我们对视网膜电路的理解，更广泛地说， 它将提供一个模板，用于剖析所有神经计算中内在属性的相对贡献。