The research objective of this project is to explore the molecular interactions between neuronal voltage-gated Ca2+ channels (VGCCs) and their presynaptic slots. The outcome of this study will serve as a gateway towards understanding the fundamental issues about neurotransmission at central nervous system (CNS) synapses.
Neurons in the CNS connect with each other at synapses. Presynaptic neurons communicate with their postsynaptic targets via synaptic transmission: the fast and well-controlled release of neurotransmitter from synaptic vesicles. Synaptic transmission at most CNS synapses is mediated by joint actions of multiple VGCCs. In her previous work Dr. Cao has demonstrated that VGCCs occupying presynaptic slots to mediate neurotransmission between hippocampal neurons. Nevertheless, the presynaptic VGCC slots remain only functionally-defined, i.e. as "virtual" slots. Here Dr. Cao proposes to explore the molecular basis of channel-slot interaction as well as the cellular localization of these slots. This project will use a multidisciplinary approach, combining techniques in electrophysiology, molecular biology, protein biochemistry as well as cellular imaging. The investigators expect to address the following aims: (1) to define the VGCC domains that interact with presynaptic slots; (2) to explore the molecular identity as well as subcellular localization of presynaptic VGCC slots. The information derived from this project will yield important insights into the fundamental mechanisms through which presynaptic VGCCs regulate CNS neurotransmission. Furthermore, the outcome of this study will increase understanding of the hippocampal-dependent cognitive processes such as learning and memory.
The research delineated in this proposal will provide opportunities for students at many levels and from diverse backgrounds to conduct independent research, preparing them for advanced scientific careers. The long-term goal is to set up Dr. Cao's laboratory as a platform for training students and postdoctoral fellows committing to both research and teaching in their future career.
