PDF(Pubmed)
Abstract：
Homeostatic plasticity stabilizes firing rates of neurons, but the pressure to restore low activity rates can significantly alter synaptic and cellular properties. Most previous studies of homeostatic readjustment to complete activity silencing in rodent forebrain have examined changes after 2 d of deprivation, but it is known that longer periods of deprivation can produce adverse effects. To better understand the mechanisms underlying these effects and to address how presynaptic as well as postsynaptic compartments change during homeostatic plasticity, we subjected mouse cortical slice cultures to a more severe 5 d deprivation paradigm. We developed and validated a computational framework to measure the number and morphology of presynaptic and postsynaptic compartments from super-resolution light microscopy images of dense cortical tissue. Using these tools, combined with electrophysiological miniature excitatory postsynaptic current measurements, and synaptic imaging at the electron microscopy level, we assessed the functional and morphological results of prolonged deprivation. Excitatory synapses were strengthened both presynaptically and postsynaptically. Surprisingly, we also observed a decrement in the density of excitatory synapses, both as measured from colocalized staining of pre- and postsynaptic proteins in tissue and from the number of dendritic spines. Overall, our results suggest that cortical networks deprived of activity progressively move toward a smaller population of stronger synapses.
摘要：
稳态可塑性稳定神经元的放电率，但是恢复低活动率的压力可以显着改变突触和细胞特性。以前大多数关于在啮齿动物前脑中完成活动沉默的体内平衡重新调整的研究都检查了剥夺两天后的变化，但是众所周知，更长的剥夺时间会产生不利影响。为了更好地理解这些影响的潜在机制，并解决在稳态可塑性过程中突触前和突触后区室如何变化，我们对小鼠皮质切片培养物进行了更严重的五天剥夺模式。我们开发并验证了一种计算框架，以从致密皮质组织的超分辨率光学显微镜图像中测量突触前和突触后隔室的数量和形态。使用这些工具，结合电生理微型兴奋性突触后电流测量，和电子显微镜水平的突触成像，我们评估了长期剥夺的功能和形态学结果.兴奋性突触在突触前和突触后都得到加强。令人惊讶的是,我们还观察到兴奋性突触的密度下降，从组织中突触前和突触后蛋白的共定位染色测量，和树突棘的数量。总的来说,我们的结果提示,活动被剥夺的皮层网络逐渐向较小的突触群移动.意义陈述新皮质切片培养物中的阻断活性在兴奋性突触产生协调的突触前和突触后变化。功能和结构分析表明，剥夺导致更少的兴奋性突触，但是每个都在突触前和突触后得到加强。这可能有助于癫痫样活动的出现。
