Activity-dependent regulation of synaptic strength by PSD-95 in CA1 neurons

作者：Zhang, Peng; Lisman, John E.^*

来源：Journal of Neurophysiology, 2012, 107(4): 1058-1066.

DOI：10.1152/jn.00526.2011

• AMPA receptor current
• metabotropic glutamate receptor
• Ca2+/calmodulin-dependent protein kinase II

Zhang P, Lisman JE. Activity-dependent regulation of synaptic strength by PSD-95 in CA1 neurons. J Neurophysiol 107: 1058-1066, 2012. First published November 23, 2011; doi:10.1152/jn.00526.2011.-CaMKII and PSD-95 are the two most abundant postsynaptic proteins in the postsynaptic density (PSD). Overexpression of either can dramatically increase synaptic strength and saturate long-term potentiation (LTP). To do so, CaMKII must be activated, but the same is not true for PSD-95; expressing wild-type PSD-95 is sufficient. This raises the question of whether PSD-95's effects are simply an equilibrium process [increasing the number of AMPA receptor (AMPAR) slots] or whether activity is somehow involved. To examine this question, we blocked activity in cultured hippocampal slices with TTX and found that the effects of PSD-95 overexpression were greatly reduced. We next studied the type of receptors involved. The effects of PSD-95 were prevented by antagonists of group I metabotropic glutamate receptors (mGluRs) but not by antagonists of ionotropic glutamate receptors. The inhibition of PSD-95-induced strengthening was not simply a result of inhibition of PSD-95 synthesis. To understand the mechanisms involved, we tested the role of CaMKII. Overexpression of a CaMKII inhibitor, CN19, greatly reduced the effect of PSD-95. We conclude that PSD-95 cannot itself increase synaptic strength simply by increasing the number of AMPAR slots; rather, PSD-95's effects on synaptic strength require an activity-dependent process involving mGluR and CaMKII.

• 出版日期2012-2