Heterogeneity of the Axon Initial Segment in Interneurons and Pyramidal Cells of Rodent Visual Cortex.
Heterogeneity of the Axon Initial Segment in Interneurons and Pyramidal Cells of Rodent Visual Cortex.
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DOI：
10.3389/fncel.2017.00332
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发表时间：
2017
影响因子：
5.3
通讯作者：
Engelhardt M
中科院分区：
文献类型：
--
作者：
Höfflin F;Jack A;Riedel C;Mack-Bucher J;Roos J;Corcelli C;Schultz C;Wahle P;Engelhardt M
在神经元中协调动作电位起始的微域是轴突起始段（AIS）。它一直被认为是一个相当均匀的域在非常近端的轴突丘，相对稳定的长度，特别是在皮质锥体细胞。然而，对其他大脑区域的研究描绘了不同的画面。在海马CA 1区，高达50%的轴突从基底树突出现。此外，在大鼠体感皮层中约30%的厚簇状V层锥体神经元中，轴突具有树突起源。因此，AIS与索马分离。最近的体外和体内研究表明，细胞兴奋性是AIS长度/位置和体树突形态的函数，破坏了AIS异质性对神经元功能的潜在重大影响。因此，我们研究了新皮层轴突形态和AIS组成，假设最初观察到的看似均匀的AIS是不够的，需要考虑到神经元细胞类型。在这里，我们在器官型培养物中生物射弹转染皮质神经元，以可视化整个神经元并结合针对AIS标记物的免疫标记对细胞类型进行分类。利用共聚焦显微镜和形态计量学分析，我们研究了轴突的起源，AIS的位置，长度，直径以及到索马体的距离。我们发现视皮层神经元中存在大量的AIS异质性，分为三组：（I）体细胞起源的轴突，其近端AIS位于轴突丘处;（II）体细胞起源的轴突，其远端AIS，AIS和索马之间存在可辨别的间隙;和（III）具有树突起源的轴突（携带轴突的树突细胞，AcD细胞）和AIS直接在轴突起源处开始或更远离该点。锥体细胞比中间神经元具有显著更长的AIS。具有垂直柱状轴突投射的中间神经元具有比所有其他细胞更远的AIS位置，其普遍表型为ACD细胞。相比之下，具有体周末梢的神经元通常显示起源于索马的轴突。我们的数据有助于新兴的理解，AIS形态是高度可变的，并可能是细胞类型的功能。
The microdomain that orchestrates action potential initiation in neurons is the axon initial segment (AIS). It has long been considered to be a rather homogeneous domain at the very proximal axon hillock with relatively stable length, particularly in cortical pyramidal cells. However, studies in other brain regions paint a different picture. In hippocampal CA1, up to 50% of axons emerge from basal dendrites. Further, in about 30% of thick-tufted layer V pyramidal neurons in rat somatosensory cortex, axons have a dendritic origin. Consequently, the AIS is separated from the soma. Recent in vitro and in vivo studies have shown that cellular excitability is a function of AIS length/position and somatodendritic morphology, undermining a potentially significant impact of AIS heterogeneity for neuronal function. We therefore investigated neocortical axon morphology and AIS composition, hypothesizing that the initial observation of seemingly homogeneous AIS is inadequate and needs to take into account neuronal cell types. Here, we biolistically transfected cortical neurons in organotypic cultures to visualize the entire neuron and classify cell types in combination with immunolabeling against AIS markers. Using confocal microscopy and morphometric analysis, we investigated axon origin, AIS position, length, diameter as well as distance to the soma. We find a substantial AIS heterogeneity in visual cortical neurons, classified into three groups: (I) axons with somatic origin with proximal AIS at the axon hillock; (II) axons with somatic origin with distal AIS, with a discernible gap between the AIS and the soma; and (III) axons with dendritic origin (axon-carrying dendrite cell, AcD cell) and an AIS either starting directly at the axon origin or more distal to that point. Pyramidal cells have significantly longer AIS than interneurons. Interneurons with vertical columnar axonal projections have significantly more distal AIS locations than all other cells with their prevailing phenotype as an AcD cell. In contrast, neurons with perisomatic terminations display most often an axon originating from the soma. Our data contribute to the emerging understanding that AIS morphology is highly variable, and potentially a function of the cell type.
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影响因子：
2.5
作者：
FARINAS, I;DEFELIPE, J
通讯作者：
DEFELIPE, J
DOI：
10.1002/cne.22006
发表时间：
2009-06-01
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Cruz DA;Lovallo EM;Stockton S;Rasband M;Lewis DA
通讯作者：
Lewis DA
DOI：
10.1523/jneurosci.4064-11.2011
发表时间：
2011-11-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Grubb MS;Shu Y;Kuba H;Rasband MN;Wimmer VC;Bender KJ
通讯作者：
Bender KJ
影响因子：
34.7
作者：
Ascoli, Giorgio A.;Alonso-Nanclares, Lidia;Anderson, Stewart A.;Barrionuevo, German;Benavides-Piccione, Ruth;Burkhalter, Andreas;Buzsaki, Gyoergy;Cauli, Bruno;DeFelipe, Javier;Fairen, Alfonso;Feldmeyer, Dirk;Fishell, Gord;Fregnac, Yves;Freund, Tamas F.;Gardner, Daniel;Gardner, Esther P.;Goldberg, Jesse H.;Helmstaedter, Moritz;Hestrin, Shaul;Karube, Fuyuki;Kisvarday, Zoltan F.;Lambolez, Bertrand;Lewis, David A.;Marin, Oscar;Markram, Henry;Munoz, Alberto;Packer, Adam;Petersen, Carl C. H.;Rockland, Kathleen S.;Rossier, Jean;Rudy, Bernardo;Somogyi, Peter;Staiger, Jochen F.;Tamas, Gabor;Thomson, Alex M.;Toledo-Rodriguez, Maria;Wang, Yun;West, David C.;Yuste, Rafael
通讯作者：
Yuste, Rafael
影响因子：
3.7
作者：
Gorba, T;Klostermann, O;Wahle, P
通讯作者：
Wahle, P