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Hippocampal Neurons In Synapse Development Mechanism

Posted on:2007-05-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:B WuFull Text:PDF
GTID:1110360185956835Subject:Neurobiology
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Synaptogenesis is a critical step in development of neural system. In thepresent study we focus on the following two topics of the synaptogenesis ofhippocampal neurons:1. BDNF-induced rapid presynaptic maturation. We found that BDNF rapidlyconverts early non-functional contacts between cultured hippocampal neurons intofunctional synapses. The increase in number of functional presynapses wasconfirmed by a marked increase in the number of depolarization-induced FM4-64puncta in the presynaptic axon. This rapid presynaptic maturation can beabolished by blocking presynaptic BDNF and Cdc42 signaling pathway or actinpolymerization. Furthermore, BDNF induces actin polymerization in presynapticterminals, as revealed by increased concentration of actin-YFP at axon boutons.Our data suggested that rapid presynaptic maturation induced by BDNF ismediated by presynaptic activation of BDNF-Cdc42 signaling, resulting inpresynaptic actin polymerization and increased glutamate release..2. The maturation of pre-and postsynaptic components of GABAergicsynapses. Neurons develop extensive axonal and dendritic arbors and formnumerous synapses. Using heterochronic coculture method, we studied thesequential events of the pre-and postsynaptic maturation. Our data showed thatfunctional synapses could be formed between young and old neurons within 24hours in culture system. However, within 72 hours of co-cultures, most of newneurons that function as presynaptic partners are glutamatergic. By usingGAD-GFP mice, we found that in GABAergic synapses, the number of newneurons that function as postsynaptic parters is much more than new neurons actas presynaptic parters. Taken together, our results suggest that the postsynapticcomponents of GABAergic synapses maturate earlier than presynaptic ones.
Keywords/Search Tags:Silent synapse, Synaptogenesis, TrkB, BDNF, Cdc42, Actin
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