Multi-Color Channelrhodopsin-Assisted Circuit Mapping of Auditory Inputs to a Novel Class of Stellate Cells in the Mouse Inferior Colliculus

多色通道视紫红质辅助听觉输入电路映射到小鼠下丘中一类新型星状细胞

• 批准号: 401540516
• 负责人: Dr. David Goyer
• 金额: --
• 依托单位: INM-6: Computational and Systems Neuroscience
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/401540516?language=en
• 关键词: Multi; Color; Channelrhodopsin; Assisted; Circuit

The inferior colliculus (IC), the midbrain center of the auditory pathway in mammals, is the first major hub of the auditory system, as virtually all information from the lower auditory brainstem nuclei converges in the IC. But despite the IC’s prominent position in the auditory system and its crucial function in the auditory pathway, we still have fundamental gaps in our knowledge of individual cell types and the organization of neural circuits in the IC. This has substantially hindered progress in understanding how the IC processes sounds. Recently, evidence has been found that the IC is a major site of plasticity following hearing loss, but it remains unclear if this plasticity is beneficial to recover normal hearing or a pathological process. A major roadblock to a deeper understanding of the IC has been that with standard techniques, it has not been possible to define distinct cell types in the IC, a prerequisite to understand how the IC can encode diverse sounds and how the IC’s output is shaped. Additionally, it is imperative to know how those different cell types are integrated in the IC’s microcircuitry, as well as how they are integrated in the ascending and descending auditory pathway. In this fellowship, these issues will be addressed by investigating how a newly identified subgroup of IC stellate cells, so-called VIP Neurons, are integrated into the IC’s circuitry. By using channelrhodopsin assisted circuit mapping, the physiological impact of synaptic inputs from commissural projections and from auditory brainstem nuclei to VIP neurons will be assessed. Additionally, it will be investigated how those inputs are integrated by the neurons and how this shapes the neurons excitability and output. This will ultimately lead to a more comprehensive understanding of how the IC detects and processes diverse sound features, and how this can be harnessed to better understand and treat hearing loss on the midbrain level.

下丘（IC）是哺乳动物听觉通路的中脑中心，是听觉系统的第一个主要枢纽，因为几乎所有来自下听觉脑干核团的信息都集中在IC。但是，尽管IC在听觉系统中的突出地位及其在听觉通路中的关键功能，我们在IC中的单个细胞类型和神经回路组织的知识方面仍然存在根本性的差距。这大大阻碍了理解IC过程如何发声的进展。最近，有证据表明IC是听力损失后可塑性的主要部位，但这种可塑性是否有利于恢复正常听力或病理过程仍不清楚。更深入地了解IC的一个主要障碍是，使用标准技术，不可能在IC中定义不同的细胞类型，这是理解IC如何编码不同声音以及IC输出如何成形的先决条件。此外，必须了解这些不同类型的细胞如何整合到IC的微电路中，以及它们如何整合到上行和下行听觉通路中。在这个奖学金，这些问题将通过调查如何一个新发现的IC星状细胞，所谓的VIP神经元，亚组集成到IC的电路来解决。通过使用通道视紫红质辅助的电路映射，将评估来自连合投射和来自听觉脑干核的突触输入对VIP神经元的生理影响。此外，还将研究这些输入如何被神经元整合，以及这如何塑造神经元的兴奋性和输出。这将最终导致更全面地了解IC如何检测和处理不同的声音特征，以及如何利用这一点来更好地了解和治疗中脑水平的听力损失。