Biphasic synaptic Ca influx arising from compartmentalized electrical signals in dendritic spines.
Biphasic synaptic Ca influx arising from compartmentalized electrical signals in dendritic spines.
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DOI：
10.1371/journal.pbio.1000190
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发表时间：
2009-09
期刊：
影响因子：
9.8
通讯作者：
Sabatini BL
中科院分区：
文献类型：
--
作者：
Bloodgood BL;Giessel AJ;Sabatini BL
树突棘分隔突触诱发的生化信号。作者表明，由棘提供的电区室化通过塑造突触钙电流的动力学而赋予相关突触额外的钙信号模式。哺乳动物主神经元上的兴奋性突触通常形成于树突棘上，树突棘由通过细颈与母树突分开的球根状头部组成。虽然激活电压门控通道在脊柱和刺激诱发的收缩脊柱颈部可以影响突触信号，电过滤的脊柱颈部的基础突触传递的贡献在很大程度上是未知的。在这里，我们使用脊柱和树突钙（Ca）成像结合2-光子激光光解笼谷氨酸评估电过滤施加的脊柱形态突触钙瞬变的影响。我们发现，在CA 1海马神经元的顶棘，棘颈创建一个障碍，电流的传播，这会导致电压下降，并导致在空间上不均匀激活电压门控钙通道（VGCC）的微米长度尺度。此外，AMPA和NMDA型谷氨酸受体（AMPAR和NMDAR，分别），共同定位在个人的脊椎头相互作用，产生两个动力学和机械上不同的阶段的突触诱发的钙内流。脊柱的快速去极化触发短暂而大的Ca电流，其幅度通过开放的AMPAR数量以分级方式调节，其持续时间通过小电导Ca激活钾（SK）通道的开放而终止。钙内流的较慢阶段独立于AMPAR开放，并由开放的NMDAR的数量和脊柱中的刺激后电位决定。双相突触Ca内流仅在AMPAR和NMDAR在单个脊柱内共同活动时发生。这些结果表明，树突棘的形态赋予相关的突触与专门的信号转导模式，并允许分级和独立的控制多个阶段的突触钙内流。哺乳动物中枢神经系统中的绝大多数兴奋性突触形成于树突棘上，树突棘是沿着树突点缀的小（< 1 fL）膜结构。每个棘的头部都被一个细颈与其母树突分开--这一形态特征直观地表明，它可能起着限制电信号和生化信号传输的作用。不幸的是，非常小的尺寸的棘，使其电特性的直接测量困难，因此，功能的影响，电区室化仍然难以捉摸。在这项研究中，我们使用时空控制的刺激，以产生钙信号内的脊椎头部和/或相邻的树突。通过比较这些测量结果，我们证明脊柱产生了专门的电信号室，这至少具有两种功能后果。首先，突触刺激，而不是类似的树突去极化，可以触发激活的电压门控钙通道内的脊柱。第二，由区室化引起的脊椎头部的电压变化塑造了突触诱发的钙内流的时间过程，使得它是双相的。因此，棘提供的电区室化允许兴奋性突触处的多种钙信号传导模式。
Dendritic spines compartmentalize synaptically-evoked biochemical signals. The authors show that electrical compartmentalization provided by a spine endows the associated synapse with additional modes of calcium signaling by shaping the kinetics of synaptic calcium currents. Excitatory synapses on mammalian principal neurons are typically formed onto dendritic spines, which consist of a bulbous head separated from the parent dendrite by a thin neck. Although activation of voltage-gated channels in the spine and stimulus-evoked constriction of the spine neck can influence synaptic signals, the contribution of electrical filtering by the spine neck to basal synaptic transmission is largely unknown. Here we use spine and dendrite calcium (Ca) imaging combined with 2-photon laser photolysis of caged glutamate to assess the impact of electrical filtering imposed by the spine morphology on synaptic Ca transients. We find that in apical spines of CA1 hippocampal neurons, the spine neck creates a barrier to the propagation of current, which causes a voltage drop and results in spatially inhomogeneous activation of voltage-gated Ca channels (VGCCs) on a micron length scale. Furthermore, AMPA and NMDA-type glutamate receptors (AMPARs and NMDARs, respectively) that are colocalized on individual spine heads interact to produce two kinetically and mechanistically distinct phases of synaptically evoked Ca influx. Rapid depolarization of the spine triggers a brief and large Ca current whose amplitude is regulated in a graded manner by the number of open AMPARs and whose duration is terminated by the opening of small conductance Ca-activated potassium (SK) channels. A slower phase of Ca influx is independent of AMPAR opening and is determined by the number of open NMDARs and the post-stimulus potential in the spine. Biphasic synaptic Ca influx only occurs when AMPARs and NMDARs are coactive within an individual spine. These results demonstrate that the morphology of dendritic spines endows associated synapses with specialized modes of signaling and permits the graded and independent control of multiple phases of synaptic Ca influx. The vast majority of excitatory synapses in the mammalian central nervous system are made onto dendritic spines, small (< 1 fL) membranous structures stippled along the dendrite. The head of each spine is separated from its parent dendrite by a thin neck – a morphological feature that intuitively suggests it might function to limit the transmission of electrical and biochemical signals. Unfortunately, the extremely small size of spines has made direct measurements of their electrical properties difficult and, therefore, the functional implications of electrical compartmentalization have remained elusive. In this study, we use spatiotemporally controlled stimulation to generate calcium signals within the spine head and/or neighboring dendrite. By comparing these measurements we demonstrate that spines create specialized electrical signaling compartments, which has at least two functional consequences. First, synaptic stimulation, but not similar dendritic depolarization, can trigger the activation of voltage-gated calcium channels within the spine. Second, voltage changes in the spine head arising from compartmentalization shape the time course of synaptically evoked calcium influx such that it is biphasic. Thus, the electrical compartmentalization provided by spines allows for multiple modes of calcium signaling at excitatory synapses.
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影响因子：
5.3
作者：
Majewska, A;Tashiro, A;Yuste, R
通讯作者：
Yuste, R
影响因子：
5.3
作者：
Nevian, T;Sakmann, B
通讯作者：
Sakmann, B
影响因子：
16.2
作者：
Enoki, Ryosuke;Hu, Yi-ling;Fine, Alan
通讯作者：
Fine, Alan
影响因子：
64.8
作者：
Losonczy, Attila;Makara, Judit K.;Magee, Jeffrey C.
通讯作者：
Magee, Jeffrey C.
DOI：
10.1073/pnas.92.18.8279
发表时间：
1995-08-29
影响因子：
11.1
作者：
DENK, W;SUGIMORI, M;LLINAS, R
通讯作者：
LLINAS, R