FUNCTIONAL ROLE OF CYTOSKELETON PROTEIN ACTIN IN SYNAPSE MATURATION AND PLASTICITY
Open Access
- Author:
- Yao, Jun
- Graduate Program:
- Biology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 18, 2007
- Committee Members:
- Gong Chen, Committee Chair/Co-Chair
Richard W Ordway, Committee Member
Zhi Chun Lai, Committee Member
Si Qiong Liu, Committee Member
Pamela J Mitchell, Committee Member - Keywords:
- actin
activity
synaptic platicity
presynaptic
silent synapse
hippocampus - Abstract:
- Long-term synaptic plasticity, which is accompanied by both functional and morphological changes of synapses, may involve not only postsynaptic potentiation, but also presynaptic enhancement. Activation of postsynaptic silent synapses has been found to contribute significantly to long-term synaptic plasticity during early developmental stage of neurons. Postsynaptic silent synapses only show NMDA receptor (NMDAR) activity but not AMPA receptor (AMPAR) activity before the induction of LTP. Postsynaptic silent synapses are activated through NMDAR-dependent insertion of AMPARs to postsynaptic density. On the other hand, presynaptic silent synapses have also been found during recent years. Presynaptic silent synapses are likely due to very low probability of neurotransmitter release. However, not like postsynaptic silent synapses, the mechanism underlying activation of presynaptic silent synapses is not well understood. Actin is an essential type of cytoskeleton protein which plays a vital role in synapse development and synaptic plasticity. Postsynaptically, actin filaments may undergo activity-dependent remodeling and play a critical role in the maintenance of LTP and stabilizing/destabilizing dendritic spines. In presynaptic terminals, actin filaments are surrounding synaptic vesicles and thus may regulate synaptic vesicle cycling. Moreover, activity-dependent presynaptic actin redistribution facilitates new synapse formation. In addition, actin was found to maintain synaptic integrity during neuronal development. The main objective of this doctoral thesis was to address the functional role of the actin during the activation of presynaptic silent synapses and long-term synaptic plasticity. Here, I have shown that repetitive spaced stimulation induced long-term synaptic plasticity in immature but not mature hippocampal neurons. Functional FM imaging and retrospective immunostaining revealed a transition of presynaptic silent boutons into active ones in response to repetitive stimulation. Electrophysiology analysis and FM imaging indicated that the activation of presynaptic silent synapses may be triggered by L-type Ca2+ channel-mediated Ca2+ influx and is dependent on downstream PKA/PKC signaling cascades, but independent of postsynaptic NMDA receptors. Moreover, inhibition of actin polymerization prevented the activation of presynaptic silent synapses, whereas promoting actin polymerization facilitates the conversion of silent to active synapses. In summary, our data suggest that the activation of presynaptic silent synapses significantly contribute to the long-term synaptic plasticity during early developmental stage of rat hippocampal neurons, and actin polymerization plays an important role in regulating such presynaptic plasticity.