Li Qin, Korte Martin, Sajikumar Sreedharan
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.
Cereb Cortex. 2016 Jun;26(6):2541-2548. doi: 10.1093/cercor/bhv084. Epub 2015 Apr 29.
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.
蛋白质合成与降解的平衡对于长期记忆存储的动态调节和实现至关重要。泛素-蛋白酶体系统（UPS）在调节增强突触处的可塑性方面的作用已得到充分研究，但其在抑制性突触群体中的作用仍不清楚。在本研究中，我们探讨了在诱导海马体长期抑制（早期-LTD）的蛋白质合成非依赖形式（突触可塑性的重要组成部分）过程中，通过抑制蛋白酶体功能来调节UPS的可能性。在此，我们表明蛋白质降解参与早期-LTD的诱导，干扰这一过程会促进早期-LTD向晚期-LTD的转变。我们在此提供证据表明，在蛋白酶体抑制的情况下，脑源性神经营养因子作为可塑性相关蛋白积累，并驱动弱抑制或增强的突触形成关联性。因此，UPS抑制通过突触标记/捕获或交叉捕获机制促进LTD，并在弱抑制或增强的突触之间建立关联性。
