Bidirectional Transport of Lysosome Related Organelles during Synapse Maintenance and Plasticity

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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.