on the mechanism of synaptic depression induced by camkiin, an endogenous inhibitor of camkii在突触camkiin引起的抑郁症的机制,camkii的内源性抑制剂.pdfVIP

On the Mechanism of Synaptic Depression Induced by CaMKIIN, an Endogenous Inhibitor of CaMKII 1 1,2 1 1,2 Camilo Gouet , Belen Aburto , Cecilia Vergara , Magdalena Sanhueza * 1 Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile, 2 Millennium Institute for Cell Dynamics and Biotechnology, University of Chile, Santiago, Chile Abstract Activity-dependent synaptic plasticity underlies, at least in part, learning and memory processes. NMDA receptor (NMDAR)- dependent long-term potentiation (LTP) is a major synaptic plasticity model. During LTP induction, Ca2+/calmodulin- dependent protein kinase II (CaMKII) is activated, autophosphorylated and persistently translocated to the postsynaptic density, where it binds to the NMDAR. If any of these steps is inhibited, LTP is disrupted. The endogenous CaMKII inhibitor proteins CaMKIINa,b are rapidly upregulated in specific brain regions after learning. We recently showed that transient application of peptides derived from CaMKIINa (CN peptides) persistently depresses synaptic strength and reverses LTP saturation, as it allows further LTP induction in previously saturated pathways. The treatment disrupts basal CaMKII-NMDAR interaction and decreases bound CaMKII fraction in spines. To unravel CaMKIIN function and to further understand CaMKII role in synaptic strength maintenance, here we more deeply investigated the mechanism of synaptic depression induced by CN peptides (CN-depression) in rat hippocampal slices. We showed that CN-depression does not require glutamatergic synaptic activity or Ca2+ signaling, thus discarding unspecific triggering of activity-dependent long-term depression (LTD) in s