Bidirectional Transport of Lysosome Related Organelles during Synapse Maintenance and Plasticity

人类的大脑非常复杂，由大约860亿个神经元和大约相同数量的非神经元细胞组成。这些神经元通过称为突触的特殊连接相互通信。非神经细胞影响这些交流。重要的是，这些细胞之间的通讯调节各种大脑功能，包括感觉、记忆存储和智力。此外，神经元内部也有交流。在神经元内部，长长的轨迹从神经元的一端移动到另一端。微观结构沿着这些轨迹移动，以调节神经元内的交流。几十年的研究已经确立了脑细胞通讯的重要性。然而，目前还不清楚这些细胞是如何影响彼此大脑功能的通讯的。在这项研究中，研究小组评估了两个神经元之间连接的形成如何相互修改以调节神经元之间的通信。为了研究这个复杂的问题，研究小组研究了一种神经系统简单得多的海懒的神经元。海参的神经元大约是人类神经元的10-100倍。具体地说，在这个项目中，研究小组使用海懒的神经元，通过成像神经元中微观结构的运动及其与记忆形成过程中神经元通讯的关系，来研究神经元内部和神经元之间的通讯。该项目还为高中生和本科生提供使用尖端技术参与研究的机会，并为佛罗里达州的中学生提供关于大脑如何连接的课程。神经元结构的复杂性，如广泛的树突分支和轴突终末，需要在细胞体及其终末之间积极地双向传输基因产物，以实现突触功能。一些研究，包括我们自己的，已经表明顺行运输(即向终末)促进突触的形成和活性依赖的突触重塑，而逆行运输(即从终末)作为信号传递到细胞核，导致转录变化。然而，这种双向运输的几个方面，如形成过程中运输的调节、动力学和机制，以及突触的维持和重塑，都知之甚少。在这个项目中，研究小组探索了已识别的海参神经元和突触的优势，通过研究溶酶体相关细胞器(LRO)在海参鳃撤退反射突触前感觉神经元中的双向运输来解决这些问题。LRO是膜结合的酸性细胞器，双向运输，参与降解途径。具体地说，该团队研究了突触前感觉神经元中LRO的双向运输在形成和维持过程中是否以及如何受到调节，以及海绵撤退反射的感觉运动神经元突触的兴奋性和抑制性可塑性的形式。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.