Circuit functions of fast-spiking interneurons in the main olfactory bulb

主嗅球中快速尖峰中间神经元的电路功能

• 批准号: 10712029
• 负责人: Shawn Denver Burton
• 金额: $ 36.67万
• 依托单位: LEHIGH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712029
• 关键词: Acute; Address; Alzheimer' s Disease; Architecture; Behavior; Biological Models; Brain; Brain region; Cells; Cholecystokinin; Code; Complex; Consensus; Data; Dendrites; Dependence; Distal; Elements; Generations; Genetic; Glutamate Receptor; Hippocampus; Histology; Human; Image; Individual; Interneuron function; Interneurons; Investigation; Ion Channel; Knowledge; Lateral; Link; Mammals; Measures; Mediating; Morphology; Mus; Neocortex; Neurons; Olfactory Pathways; Output; Parkinson Disease; Pattern; Perception; Peripheral; Pharmacology; Prevalence; Process; Property; Recurrence; Regulation; Rodent; Role; Sensory; Sensory Deprivation; Signal Transduction; Site; Slice; Smell Perception; Stimulus; Study models; Synapses; Target Populations; Testing; Viral; Whole-Cell Recordings; Work; cell type; excitatory neuron; gamma-Aminobutyric Acid; granule cell; inhibitory neuron; insight; neocortical; nerve supply; nervous system disorder; neural; olfactory bulb; organizational structure; postsynaptic; reconstruction; sensory input; simulation; synaptic inhibition

PROJECT SUMMARY/ABSTRACT The olfactory system is critical to several aspects of behavior and survival in mammals, including humans. The olfactory bulb is the first processing station of the olfactory system and constitutes an exceptional model system for the study of neural coding, capable of encoding a highly complex sensory space within a compact and well- organized structure. Understanding local circuit computation within the olfactory bulb will thus provide key insight into fundamental principles of brain function. Broad perturbation of synaptic inhibition within the olfactory bulb significantly disrupts projection mitral/tufted cell synchronization and olfactory-guided behavior, underscoring a central role of inhibitory interneurons in local circuit computation. In contrast to other regions of the brain such as neocortex and hippocampus, however, fundamental understanding of how the diverse inhibitory interneurons within the olfactory bulb specifically support neural coding has remained elusive, with detailed knowledge of how unitary synaptic interactions contribute to the precise regulation of mitral/tufted cell spike timing in particular lacking. To advance understanding of local circuit computation and neural coding in the olfactory bulb, this project will therefore directly examine unitary synaptic interactions between mitral/tufted cells and a highly-conserved but understudied class of fast-spiking interneurons, using whole-cell pair recordings in acute mouse brain slices together with pharmacology, morphological reconstruction, immunostaining, and simulations. Investigation will specifically address three aims: 1) determine how fast-spiking interneurons regulate mitral/tufted cell spike timing, 2) determine how dendritic computation supports fast-spiking interneuron function, and 3) determine how fast-spiking interneuron signaling adapts with neural activity.

项目概要/摘要 嗅觉系统对于包括人类在内的哺乳动物的行为和生存的多个方面至关重要。这 嗅球是嗅觉系统的第一个处理站，构成了一个特殊的模型系统 用于神经编码的研究，能够在紧凑且良好的环境中编码高度复杂的感觉空间 有组织的结构。因此，了解嗅球内的局部电路计算将提供关键的见解 深入了解大脑功能的基本原理。嗅球内突触抑制的广泛扰动 显着破坏投射二尖瓣/簇状细胞同步和嗅觉引导行为，强调 抑制性中间神经元在局部电路计算中的核心作用。与大脑的其他区域相比， 然而，作为新皮质和海马体，对不同的抑制性中间神经元如何发挥作用的基本了解 嗅球内具体支持的神经编码仍然难以捉摸，详细了解如何 单一突触相互作用尤其有助于二尖瓣/簇状细胞尖峰时间的精确调节 缺乏。为了加深对嗅球局部电路计算和神经编码的理解，该项目 因此，将直接检查二尖瓣/簇状细胞和高度保守的细胞之间的单一突触相互作用 但利用急性小鼠脑切片中的全细胞对记录，研究了快速尖峰中间神经元的类别 以及药理学、形态重建、免疫染色和模拟。调查将 具体解决三个目标：1）确定快速尖峰中间神经元如何调节二尖瓣/簇状细胞尖峰 计时，2) 确定树突计算如何支持快速尖峰中间神经元功能，以及 3) 确定如何 快速尖峰的中间神经元信号传导适应神经活动。