NSF Award
1453799
One of the fundamental questions in neuroscience concerns memory-- how it works and why it goes wrong. Decades of research have identified that, at the cellular level, formation of new synaptic connections and remodeling of pre-existing synaptic connections are critical for memory formation. However, very little is known about how long-term memories are stored at specific synapses in the brain. To address this fundamental and unresolved problem, the investigators will take advantage of the large, identified neurons of the well-studied gill-withdrawal reflex circuitry of the sea snail Aplysia. The key components of this neural circuitry can easily be identified, isolated, and cultured to generate neural circuits in a dish that are amenable to investigation at the single-cell and subcellular level. Integrating synapse-specific physiological measurements with state-of-the-art live-cell imaging and tools for single-cell genomics analysis, the investigators will study the role of axonal transport in generating and maintaining synapse-specific long-term memory. The results from this work will yield novel insights into the molecular mechanisms that underlie the synapse-specific nature of long-term memories. As part of this project, high school and undergraduate students from diverse backgrounds will receive mentoring and be actively involved in various aspects of this study. Furthermore, a neuroscience inquiry-based lesson that involves the training of middle and high school students and middle school teachers will be developed and implemented. <br/><br/>The proposed project investigates the molecular and cellular mechanisms underlying synapse-specific long-term memory storage. First, the project will assess whether and how gene products such as proteins and mRNAs are transported from the cell-body of neurons to specific synapses. Because the molecular motor protein kinesin mediates the transport of gene products from the cell-body, kinesin movement to synapses during memory formation and maintenance will be studied using advanced quantitative live-cell imaging microscopy. Second, mRNAs transported to specific synaptic compartments by kinesin will be identified using single-cell genomics tools. Third, whether and how the synapse communicates back to the cell-body during memory formation will be studied by characterizing the molecular motor protein dynein that moves from the synapse to the cell body. Taken together, these studies will bring novel molecular and mechanistic insights into understanding long-term memory storage and help identify specific mRNAs localized to specific synaptic compartments for storing long-term memories.
