Walker Alison S, Neves Guilherme, Grillo Federico, Jackson Rachel E, Rigby Mark, O'Donnell Cian, Lowe Andrew S, Vizcay-Barrena Gema, Fleck Roland A, Burrone Juan
Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom.
Department of Computer Science, University of Bristol, Bristol BS8 1UB, United Kingdom.
Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):E1986-E1995. doi: 10.1073/pnas.1607462114. Epub 2017 Feb 16.
Neurons receive a multitude of synaptic inputs along their dendritic arbor, but how this highly heterogeneous population of synaptic compartments is spatially organized remains unclear. By measuring -methyl-d-aspartic acid receptor (NMDAR)-driven calcium responses in single spines, we provide a spatial map of synaptic calcium signals along dendritic arbors of hippocampal neurons and relate this to measures of synapse structure. We find that quantal NMDAR calcium signals increase in amplitude as they approach a thinning dendritic tip end. Based on a compartmental model of spine calcium dynamics, we propose that this biased distribution in calcium signals is governed by a gradual, distance-dependent decline in spine size, which we visualized using serial block-face scanning electron microscopy. Our data describe a cell-autonomous feature of principal neurons, where tapering dendrites show an inverse distribution of spine size and NMDAR-driven calcium signals along dendritic trees, with important implications for synaptic plasticity rules and spine function.
神经元在其树突分支上接收大量突触输入,但这种高度异质性的突触小室群体在空间上是如何组织的仍不清楚。通过测量单个棘突中N-甲基-D-天冬氨酸受体(NMDAR)驱动的钙反应,我们提供了沿海马神经元树突分支的突触钙信号空间图谱,并将其与突触结构测量相关联。我们发现,量子化的NMDAR钙信号在接近变细的树突末端时,其幅度会增加。基于棘突钙动力学的隔室模型,我们提出钙信号的这种偏向分布受棘突大小逐渐的、距离依赖性下降的控制,我们使用连续块面扫描电子显微镜对其进行了可视化。我们的数据描述了主神经元的一种细胞自主特征,即逐渐变细的树突在树突树上显示出棘突大小和NMDAR驱动的钙信号的反向分布,这对突触可塑性规则和棘突功能具有重要意义。