Molecular characterization of neuronal subtype diversity

构成神经系统的复杂电路伴随着大量的细胞多样性。了解区分不同类型神经细胞的功能和分子特征是神经科学的核心问题。我们的研究重点是解决视网膜神经元间细胞类型多样性的机制，被称为双极细胞。视网膜双极细胞是一类异质的、功能复杂的中间神经元，对接收、处理和传递视觉信号至关重要。至少有10种形态不同的双极细胞类型已经被描述，并且在小鼠和人类中高度保守。这些细胞类型具有独特的生理特性和基因表达模式，表明其功能和维持背后有不同的调节机制。虽然电生理和基因靶向方法推动了我们对视网膜神经生物学基本方面的理解，但我们对神经元亚型水平的视网膜功能和电路的理解受到了识别和区分不同亚型能力的挑战。本研究计划的目标是利用分子和转基因策略，使我们能够阐明视网膜双极性亚型的分子和功能多样性。这项研究计划的目的是利用新颖而强大的方法来阐明视网膜回路形成和视觉信号的机制。我的实验室拥有专业知识和协作投入，可以在这一领域取得重大进展。本研究将为了解视网膜视觉信号及相关疾病提供基础知识。此外，这项工作将作为神经系统其他部分神经元亚型多样性的模型。

The complex circuitry that makes up the nervous system is accompanied by a tremendous amount of cellular diversity. Understanding the functional and molecular characteristics that distinguish one neuronal cell type from another is a central problem in neuroscience. Our research is focused on addressing the mechanisms that underlie cell type diversity in an interneuronal cell class with the retina, known as bipolar cells. Retinal bipolar cells comprise a heterogeneous and functionally complex class of interneurons essential for receiving, processing and transmitting visual signals. At least 10 morphologically distinct bipolar cell types have been described and are highly conserved in mice and humans. These cell types possess unique physiological properties and gene expression patterns, indicating that distinct regulatory mechanisms underlie their function and maintenance. While electrophysiological and gene-targeting approaches have driven our understanding of fundamental aspects of retinal neurobiology, our understanding of retinal function and circuitry at the neuronal subtype level has been challenged by the ability to identify and discriminate between different subtypes. The goal of this research program is to utilize molecular and transgenic strategies that will enable us to elucidate the molecular and functional diversity of retinal bipolar subtypes. The aims of this research program utilize novel and powerful approaches that will to shed light on the mechanisms underlying retinal circuit formation and visual signaling. My laboratory has the expertise and collaborative input to make significant progress in this area. This research will provide basic knowledge for understanding retinal visual signaling and related disease. In addition, this work will serve as a model for neuronal subtype diversity in other parts of the nervous system.