Zhang Yong, Cudmore Robert H, Lin Da-Ting, Linden David J, Huganir Richard L
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nat Neurosci. 2015 Mar;18(3):402-7. doi: 10.1038/nn.3936. Epub 2015 Feb 2.
Regulation of AMPA receptor (AMPAR) membrane trafficking is critical for synaptic plasticity, as well as for learning and memory. However, the mechanisms of AMPAR trafficking in vivo remain elusive. Using in vivo two-photon microscopy in the mouse somatosensory barrel cortex, we found that acute whisker stimulation led to a significant increase in the intensity of surface AMPAR GluA1 subunit (sGluA1) in both spines and dendritic shafts and a small increase in spine size relative to prestimulation values. Interestingly, the initial spine properties biased spine changes following whisker stimulation. Changes in spine sGluA1 intensity were positively correlated with changes in spine size and dendritic shaft sGluA1 intensity following whisker stimulation. The increase in spine sGluA1 intensity evoked by whisker stimulation was NMDA receptor dependent and long lasting, similar to major forms of synaptic plasticity in the brain. In this study we were able to observe experience-dependent AMPAR trafficking in real time and characterize, in vivo, a major form of synaptic plasticity in the brain.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPAR)膜转运的调控对于突触可塑性以及学习和记忆至关重要。然而,AMPAR在体内的转运机制仍不清楚。利用小鼠体感桶状皮质的体内双光子显微镜技术,我们发现急性触须刺激导致棘突和树突干中表面AMPAR GluA1亚基(sGluA1)的强度显著增加,并且相对于刺激前值,棘突大小有小幅增加。有趣的是,最初的棘突特性使触须刺激后的棘突变化产生偏差。触须刺激后,棘突sGluA1强度的变化与棘突大小和树突干sGluA1强度的变化呈正相关。触须刺激引起的棘突sGluA1强度增加是NMDA受体依赖性的且持久,类似于大脑中主要形式的突触可塑性。在本研究中,我们能够实时观察依赖经验的AMPAR转运,并在体内表征大脑中一种主要形式的突触可塑性。