Functional Dissection of Glutamatergic Synapses: From Contact to Evoked Neurotransmission

Abstract

Recent studies have made remarkable progress toward understanding the cellular and molecular mechanisms of synapse formation in the central nervous system. It has been demonstrated that presynaptic vesicles and proteins are preassembled into packets and transported along axons to newly formed axon-dendritic sites. Similarly, postsynaptic glutamate receptor subunits have also been found in mobile transport packets and recruited to nascent axon-dendritic sites. Although these imaging studies suggest a rapid time course for the formation of a new synapse (minutes to hours rather than days to weeks), it is unknown whether active neurotransmission is occurring across these nascent synapses. This proposal takes a novel approach by using a single-synapse-recording system to monitor the functional appearance of evoked synaptic transmission at individual glutamatergic synapses in rat hippocampal culture. Local signaling pathways during synaptic remodeling of nascent synapses will be explored by a combination of patch clamp recording, fluorescence imaging, and molecular biology techniques. These studies should provide a clear view of the functional time course of synaptogenesis at central synapses. It will improve our understanding about how neural networks are built and remodeled during brain development.

The PI's long-term career goal is to explore the cellular and molecular mechanisms of learning and memory, focusing on synaptogenesis and synaptic plasticity. This proposal aims at a better understanding of functional formation of synapses, the fundamental units of our brain. Synaptogenesis at early developmental stages helps wire and integrate individual neurons into functional circuits. At later stages, new synapses form continuously while others are eliminated from the synaptic network. This plasticity of synaptic connections is believed to be important during learning and memory. Therefore, the Chen laboratory's research on functional synapse formation and synaptic remodeling will broadly enhance the understanding of neural development and learning and memory. One important element of this proposal involves training of graduate and undergraduate students, as well as postdoctoral researchers. Insight gained through this research will also be integrated into the PI's teaching of Developmental Neurobiology course offering to graduate and undergraduate students.