Understanding the mechanisms of synapse formation using trans-synaptic labeling

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The fundamental mechanisms regulating the development of brain connections are highly explored but remain unknown. Neural connections, known as synapses, are specialized structures that mediate communication between nerve cells (neurons). These structures are important to study because they are the basic substrates from which process such as learning and memory is generated. Synapse formation is still not well understood despite the generation of sophisticated tools that allow scientists to assess their function. Current knowledge of synapse formation is based upon methods that provide a cross-sectional time window to study the developmental process or assess the functionality of synapses. However, synapse formation does not occur randomly between neurons and is a regulated, dynamic process that occurs over time, which is not possible to observe using currently available tools. The main focus of my lab is to study mechanisms of synapse formation including their rate of development and specificity, by overcoming limitations using a combination of novel genetic tools and high-resolution microscopy. Our short-term goals are to use an innovative technique named TRANS-SYNAPTIC LABELING, which makes use of a safely modified Rabies virus that labels neurons making synapses in real time with fluorescence. Using this method, we will now be able to ask which neurons form synapses with each other (specificity), at what time scale (rate), and determine the complete connectivity map of an individual neuron, all of which has never been possible. For our long-term goals, we will build upon these newly developed assays and examine molecular signaling pathways that regulate these processes. The knowledge gained from these studies will directly benefit the neurodevelopment field since our work will provide new knowledge and mechanisms by which synapse formation occurs. This will ultimately lead to a better understanding of how the brain develops.