Vaidya Rohit M, Zhang Jiahao, Nall Duncan, Lee Yongjae, Chang Kim Eung, Ma Donghan, Huang Fang, Nonaka Hiroshi, Kiyonaka Shigeki, Hamachi Itaru, Jung Chung Hee, Selvin Paul R
Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign; Urbana, IL, 61801, USA.
Dept. of Physics, University of Illinois at Urbana-Champaign; Urbana, IL, 61801, USA.
bioRxiv. 2024 Jul 23:2024.07.22.604547. doi: 10.1101/2024.07.22.604547.
Synaptic AMPA receptors (AMPARs) on neuronal plasma membranes are correlated with learning and memory. Using a unique labeling and super-resolution imaging, we have visualized the nanoscale synaptic and extra-synaptic organization of native AMPARs for the first time in mouse brain slices as a function of brain region and tauopathy. We find that the fraction of surface AMPARs organized in synaptic clusters is two-times smaller in the hippocampus compared to the motor and somatosensory cortex. In 6 months old PS19 model of tauopathy, synaptic and extrasynaptic distributions are disrupted in the hippocampus but not in the cortex. Thus, this optimized super-resolution imaging tool allows us to observe synaptic deterioration at the onset of tauopathy before apparent neurodegeneration.
神经元质膜上的突触α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPARs）与学习和记忆相关。通过独特的标记和超分辨率成像，我们首次在小鼠脑切片中可视化了天然AMPARs的纳米级突触和突触外组织，这是脑区和tau蛋白病的函数。我们发现，与运动和体感皮层相比，海马体中组织成突触簇的表面AMPARs比例小两倍。在6个月大的tau蛋白病PS19模型中，海马体中的突触和突触外分布受到破坏，但皮层中没有。因此，这种优化的超分辨率成像工具使我们能够在明显的神经退行性变之前观察到tau蛋白病发作时的突触退化。
