The proper development of neural connections, called synapses, is critical for normal brain function; abnormal synapse formation impairs brain development, and renders the nervous system dysfunctional in all organisms including humans. Synapses work by two different mechanisms: those that use particular molecules to communicate with other nerve cells (chemical synapses), and those that communicate through specialized electrical connections between nerve cells (electrical synapses). Most of the mechanism that chemical synapses use to form and function normally have been well-studied, but much less is known about the mechanisms guiding the initial formation of electrical synapses. Results from this project will identify key molecular events that are critical for the successful formation of functional electrical synapses. The identification of these mechanisms will advance the understanding of how networks of nerve cells develop, and provide possible new avenues for the treatment of nervous system disorders. This research will also provide training opportunities for graduate, undergraduate, and high school student participants; individuals filling these positions will be recruited from groups traditionally underserved in STEM fields. The project will additionally support an annual neuroscience workshop to promote STEM education through the Youth Exploring Science program at the St. Louis Science Center.
Synapses are specialized structures that serve as the fundamental unit for all nervous system functions. There are two main types of synaptic communication in animals: chemical (transmitter-mediated) and electrical (gap junction channel-mediated). In contrast to our extensive knowledge of the formation of chemical synapses, very little is known about the basic mechanisms governing the formation of electrical synapses (electrosynaptogenesis). This leaves a large gap in the fundamental knowledge of how animal nervous systems are developed. The objective of this study is to investigate the roles and mechanisms of neurotrophic factors in regulating electrosynaptogenesis using an in vitro soma-soma synapse model from pond snail (Lymnaea stagnalis) brains. We will culture individual gap-junction-forming neurons and monitor the neurotrophic factor-induced cellular and molecular events (neural activity, cellular messengers, and signaling pathways) throughout the course of electrosynaptogenesis. We will also determine whether neurotrophic factors act to induce synthesis and/or release of neurotransmitters and promote neurotransmitter-receptor interactions to facilitate electrosynaptogenesis. Synapse formation will be verified by electrophysiology and neurochip (long-term, non-invasive) techniques. This study will improve the fundamental understanding of the molecular, cellular, and synaptic basis of electrosynaptogenetic events that occur in all animals.
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.
