Role of the Ca2+ /calmodulin kinase II (CaMKII) and its interaction with the NMDA receptor in homeostatic synaptic plasticity

Abstract

Homeostatic synaptic plasticity (HSP) is a diverse group of slow compensatory mechanisms allowing neurons to regulate their synaptic inputs according to network activity and is believed to contribute to the stabilization of Hebbian forms of synaptic plasticity (i.e., LTP, LTD). We previously described a form of HSP that develops between 5 to 13 hours after slicing rat hippocampus and is presumably triggered by the decrease in circuit activity due to deafferentation. To assess the mechanism of HSP, we investigated a possible role of CaMKII and its interaction with the glutamatergic NMDA receptor (NMDAR). CaMKII/NMDAR interaction has been extensively investigated in the context of LTP and may be a potential orchestrator of HSP. We show that after a pharmacological disassembly of this complex and transient inhibition of CaMKII, postsynaptic adaptations do not occur on time. Additionally, this form of HSP may be occurring in a context of altered hippocampal connectivity, as evoked excitatory postsynaptic current (EPSC) displayed polyphasic shapes, which may reflect the increased polysynaptic activity commonly observed in other models of neuronal deafferentation. In the presence of high concentrations of divalent cations used to isolate monophasic EPSC, we obtained preliminary evidence indicating that this HSP process preserves the AMPAR/NMDAR transmission and the GluN2B/GluN2A-NMDAR subunits ratio, indicating that this HSP process does not alter the information content of synapses. Finally, we tested whether this process involves the insertion of GluA1-homomeric AMPARs into synapses, which has been previously related to some rapid forms of HSP. However, we did not found evidence supporting this possibility.