Ubiquitin-Proteasome System Inhibition Promotes Long-Term Depression and Synaptic Tagging/Capture.
A balance of protein synthesis and degradation is critical for the dynamic regulation and implementation of long-term memory storage. The role of the ubiquitin-proteasome system (UPS) in regulating the plasticity at potentiated synapses is well studied, but its roles in depressed synaptic populations remain elusive. In this study, we probed the possibility of regulating the UPS by inhibiting the proteasome function during the induction of protein synthesis-independent form of hippocampal long-term depression (early-LTD), an important component of synaptic plasticity. Here, we show that protein degradation is involved in early-LTD induction and interfering with this process facilitates early-LTD to late-LTD. We provide evidence here that under the circumstances of proteasome inhibition brain-derived neurotrophic factor is accumulated as plasticity-related protein and it drives the weakly depressed or potentiated synapses to associativity. Thus, UPS inhibition promotes LTD and establishes associativity between weakly depressed or potentiated synapses through the mechanisms of synaptic tagging/capture or cross-capture.
Division of Cellular Neurobiology, Zoological Institute, TU Braunschweig, Braunschweig D-38106, Germany.
Qin
Q
Li
Division of Cellular Neurobiology, Zoological Institute, TU Braunschweig, Braunschweig D-38106, Germany.
Martin
M
Korte
Division of Cellular Neurobiology, Zoological Institute, TU Braunschweig, Braunschweig D-38106, Germany.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.|Neurobiology/Ageing Programme, National University of Singapore, Singapore 117456.
Sreedharan
S
Sajikumar
D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology; D059748:Proteolysis / Q000187:drug effects; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques; D025801:Ubiquitin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D061988:Proteasome Inhibitors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
long-term depression; protein degradation; protein synthesis; synaptic tagging; synaptic tagging and capture