Masoli Stefano, D'Angelo Egidio
Department of Brain and Behavioral Sciences, University of PaviaPavia, Italy.
Brain Connectivity Center, C. Mondino National Neurological InstitutePavia, Italy.
Front Cell Neurosci. 2017 Sep 13;11:278. doi: 10.3389/fncel.2017.00278. eCollection 2017.
The dendritic processing in cerebellar Purkinje cells (PCs), which integrate synaptic inputs coming from hundreds of thousands granule cells and molecular layer interneurons, is still unclear. Here we have tested a leading hypothesis maintaining that the significant PC output code is represented by burst-pause responses (BPRs), by simulating PC responses in a biophysically detailed model that allowed to systematically explore a broad range of input patterns. BPRs were generated by input bursts and were more prominent in Zebrin positive than Zebrin negative (Z+ and Z-) PCs. Different combinations of parallel fiber and molecular layer interneuron synapses explained type I, II and III responses observed . BPRs were generated intrinsically by Ca-dependent K channel activation in the somato-dendritic compartment and the pause was reinforced by molecular layer interneuron inhibition. BPRs faithfully reported the duration and intensity of synaptic inputs, such that synaptic conductance tuned the number of spikes and release probability tuned their regularity in the millisecond range. Interestingly, the burst and pause of BPRs depended on the stimulated dendritic zone reflecting the different input conductance and local engagement of voltage-dependent channels. Multiple local inputs combined their actions generating complex spatio-temporal patterns of dendritic activity and BPRs. Thus, local control of intrinsic dendritic mechanisms by synaptic inputs emerges as a fundamental PC property in activity regimens characterized by bursting inputs from granular and molecular layer neurons.
小脑浦肯野细胞(PCs)中的树突处理过程仍不清楚,该过程整合了来自数十万颗粒细胞和分子层中间神经元的突触输入。在这里,我们通过在一个生物物理细节模型中模拟PC反应来测试一个主要假设,该假设认为显著的PC输出代码由爆发-暂停反应(BPRs)表示,这个模型允许系统地探索广泛的输入模式。BPRs由输入爆发产生,在Zebrin阳性PCs中比Zebrin阴性(Z+和Z-)PCs中更显著。平行纤维和分子层中间神经元突触的不同组合解释了观察到的I型、II型和III型反应。BPRs在体-树突区由钙依赖性钾通道激活内在产生,并且暂停通过分子层中间神经元抑制得到加强。BPRs忠实地报告了突触输入的持续时间和强度,使得突触电导调节尖峰数量,释放概率调节它们在毫秒范围内的规律性。有趣的是,BPRs的爆发和暂停取决于受刺激的树突区域,反映了不同的输入电导和电压依赖性通道的局部参与。多个局部输入联合它们的作用,产生复杂的树突活动时空模式和BPRs。因此,在以颗粒层和分子层神经元的爆发性输入为特征的活动模式中,突触输入对树突内在机制的局部控制成为PC的一个基本特性。