期刊
JOURNAL OF NEUROSCIENCE
卷 27, 期 20, 页码 5363-5372出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0164-07.2007
关键词
synaptic plasticity; p21-activated kinase; cofilin; dendritic spines; postsynaptic density; phosphorylation
资金
- NIA NIH HHS [AG00358] Funding Source: Medline
- NINDS NIH HHS [NS45260, NS37799, NS051823, R01 NS051823, R01 NS037799, P01 NS045260] Funding Source: Medline
Stabilization of long-term potentiation ( LTP) is commonly proposed to involve changes in synaptic morphology and reorganization of the spine cytoskeleton. Here we tested whether, as predicted from this hypothesis, induction of LTP by theta-burst stimulation activates an actin regulatory pathway and alters synapse morphology within the same dendritic spines. TBS increased several fold the numbers of spines containing phosphorylated ( p) p21-activated kinase ( PAK) or its downstream target cofilin; the latter regulates actin filament assembly. The PAK/cofilin phosphoproteins were increased at 2 min but not 30 s post-TBS, peaked at 7 min, and then declined. Double immunostaining for the postsynaptic density protein PSD95 revealed that spines with high pPAK or pCofilin levels had larger synapses ( +60-70%) with a more normal size frequency distribution than did neighboring spines. Based on these results and simulations of shape changes to synapse-like objects, we propose that theta stimulation markedly increases the probability that a spine will enter a state characterized by a large, ovoid synapse and that this morphology is important for expression and later stabilization of LTP.
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