Scullin Chessa S, Schiess Adrian R B, Donald Partridge L
Department of Neurosciences, University of New Mexico, Albuquerque, NM 871311, United States; Physical Biosciences, Lawrence Berkeley National Laboratories, Berkeley, CA 94720, United States.
Department of Neurosciences, University of New Mexico, Albuquerque, NM 871311, United States; Biosciences, Sandia National Labs, Albuquerque, NM 87123, United States.
Brain Res. 2015 Oct 5;1622:22-35. doi: 10.1016/j.brainres.2015.06.013. Epub 2015 Jun 20.
In order to explore short-term facilitation of the Schaffer collateral to CA1 synapse in mouse hippocampal brain slices, we measured the time course of the decay of the peak amplitude of successive EPSCs during progressive MK-801-dependent block (PMDB) of NMDAR responses to paired (R1 and R2) stimuli. We made the unexpected observation that the R2 response exhibited a slower PMDB decay constant than that of the R1 response. This indicated that the facilitated R2 response engages release sites with NMDARs that are protected from opening and consequent MK-801 block during the basal R1 response. We then utilized conditions that affect synaptic glutamate distribution to dissect the components of the distinct PMDB decay constants of the first and second of paired pulses. While extra-synaptic NMDARs and glutamate transporters appear to play only minor roles in the differences of the PMDB decay constant, we showed important roles for the R1 response itself and for glutamate diffusion in determining the PMDB decay constant of R2. We used a simple computational model with realistic parameters that allowed us to predict the time course of R2 decay based on the R1 decay time course.
为了探究小鼠海马脑片中从Schaffer侧支到CA1突触的短期易化作用，我们在NMDAR对配对（R1和R2）刺激的反应进行逐步MK - 801依赖性阻断（PMDB）期间，测量了连续EPSC峰值幅度衰减的时间进程。我们意外地观察到，R2反应的PMDB衰减常数比R1反应的要慢。这表明，易化后的R2反应所涉及的释放位点与NMDAR相关，这些NMDAR在基础R1反应期间受到保护，不会开放以及随后被MK - 801阻断。然后，我们利用影响突触谷氨酸分布的条件，剖析配对脉冲中第一个和第二个脉冲不同PMDB衰减常数的组成部分。虽然突触外NMDAR和谷氨酸转运体在PMDB衰减常数的差异中似乎仅起次要作用，但我们发现R1反应本身以及谷氨酸扩散在决定R2的PMDB衰减常数方面起着重要作用。我们使用了一个具有实际参数的简单计算模型，该模型使我们能够根据R1衰减的时间进程预测R2衰减的时间进程。
