Bidirectional Transport of Lysosome Related Organelles during Synapse Maintenance and Plasticity

突触维持和可塑性过程中溶酶体相关细胞器的双向运输

• 批准号: 2026993
• 负责人: Sathyanarayanan Puthanveettil
• 金额: $ 106万
• 依托单位: The Scripps Research Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2026993&HistoricalAwards=false
• 关键词: Bidirectional; Transport; Lysosome; Related; Organelles

The human brain is extraordinarily complex consisting of about 86 billion neurons and about the same number of non-neuronal cells. The neurons communicate with each other through specialized junctions known as synapses. The non-neuronal cells influence these communications. Importantly communications between these cells mediate various brain functions including sensory perception, memory storage, and intelligence. Furthermore, there is also communication within neurons. Inside neurons, long tracks are traveling from one end of the neuron to the other end. Microscopic structures move along these tracks for mediating communication within neurons. Decades of research have established the significance of brain cell communications. However, it is not well understood precisely how these cells influence each other’s communications for brain functions. In this study, the investigative team assesses how the formation of connections between two neurons modifies each other for mediating neuronal communications. To study this complex problem, the team studies neurons of a sea slug that has a much simpler nervous system. Neurons of sea slug are about 10-100 times larger than human neurons. Specifically, using the neurons of sea slug, the team in this project studies communication within neurons and between neurons by imaging the movement of microscopic structures in neurons and its relation to neuronal communication during memory formation. The project also offers high school and undergraduate students to participate in research using cutting-edge techniques, and includes lessons on how the brain is wired for middle school students in Florida.The complexity of neuronal architecture such as the extensive dendritic branching and axonal terminals necessitates active bidirectional transport of gene products between the cell body and its terminals for synapse function. Several studies, including our own, have indicated that anterograde transport (i.e., towards terminals) facilitates synapse formation and activity-dependent remodeling of synapses, while retrograde transport (i.e., from terminals) serves as signals to the nucleus resulting in transcriptional changes. However, several aspects of this bi-directional transport, such as the regulation, dynamics, and mechanisms of transport during formation, and maintenance and remodeling of synapses are poorly understood. In this project, exploring the advantages of the identified neurons and synapses of the sea slug Aplysia californica, the investigative team addresses these questions by studying the bidirectional transport of lysosome-related organelles (LROs) in presynaptic sensory neurons of Aplysia gill withdrawal reflex. LROs are membrane-bound acidic organelles transported bidirectionally and are involved in degradative pathways. Specifically, the team studies whether and how bidirectional transport of LROs in presynaptic sensory neurons is regulated during formation and maintenance, and excitatory and inhibitory forms of plasticity at sensory-motor neuron synapses of Aplysia gill withdrawal reflex.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

人脑非常复杂，由约860亿个神经元和大约相同数量的非神经元细胞组成。神经元通过称为突触的专业连接处相互通信。非神经元细胞会影响这些通信。重要的是，这些细胞之间的通信介导了各种大脑功能，包括感觉知觉，记忆存储和智力。此外，神经元内也有通信。在神经元内，长音轨从神经元的一端传播到另一端。微观结构沿着这些轨道移动，以介导神经元内的通信。数十年的研究确定了脑细胞通信的重要性。但是，这些细胞如何影响彼此的脑功能通信尚不清楚。在这项研究中，调查小组评估了两个神经元之间的连接形成如何互相修饰以介导神经元通信。为了研究这个复杂的问题，小组研究了具有更简单神经系统的海s神经元。海s神经元比人神经元大约10-100倍。具体而言，使用Sea Slug的神经元，该项目中的团队通过对神经元中的显微镜结构的运动进行成像，研究神经元内和神经元之间的交流，以及在记忆形成过程中其与神经元通信的关系。该项目还为高中和本科生提供了使用尖端技术参与研究的研究，并包括有关佛罗里达州中学生的大脑如何连接的经验教训。包括我们自己在内的几项研究表明，顺行传输（即向终端）促进突触的形成和活动依赖于突触的重塑，而逆行转运（即来自末端）用作传递转录变化的核的信号。然而，对这种双向运输的几个方面，例如在形成过程中的调节，动力学和运输机制，以及对突触的维护和重塑。在该项目中，探讨了加利福尼亚州Slug Aplysia aplysia aplysia aplysia aplysia aplysia aplysia的优势，通过研究溶酶体相关细胞器（LROS）在Aplysia Gills Giill戒断反射反射的双向感官神经元中的双向转运来解决这些问题。 LROS是双向运输的膜结合的酸性细胞器，并参与降解途径。具体而言，团队研究LRO在形成和维护期间是否以及如何在感觉运动和抑制形式的锻炼和抑制形式的可塑性形式受到感觉运动神经元突触中的锻炼和抑制形式的调节。这是NSF的法定任务和审查均通过评估的支持。