Type 2 K+–Cl− cotransporter is preferentially recruited to climbing fiber synapses during development and the stellate cell‐targeting dendritic zone at adulthood in cerebellar Purkinje cells
Type 2 K+–Cl− cotransporter is preferentially recruited to climbing fiber synapses during development and the stellate cell‐targeting dendritic zone at adulthood in cerebellar Purkinje cells
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DOI：
10.1111/ejn.12076
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发表时间：
2013-02
影响因子：
3.4
通讯作者：
Issei Kawakita;M. Uchigashima;Kohtarou Konno;T. Miyazaki;Miwako Yamasaki;Masahiko Watanabe
中科院分区：
文献类型：
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作者：
Issei Kawakita;M. Uchigashima;Kohtarou Konno;T. Miyazaki;Miwako Yamasaki;Masahiko Watanabe
出生后神经元中2型K+ -Cl -共转运体（KCC2）的表达将Cl -平衡电位降低到比静息电位更负的值，从而将Cl -渗透性GABAA和甘氨酸受体的作用从兴奋性转化为抑制性。在本研究中，我们研究了KCC2在小鼠小脑中的时空表达，特别关注浦肯野细胞（PCs）。首先，我们确认了KCC2在小脑中的基本表达谱，即神经元特异性表达、体树突分布和出生后上调。我们还发现，在出生后的第二周和第三周，当PCs的周围神经支配从CFs转移到篮细胞轴突（BAs）时，以及当单个获胜CFs从体细胞转移到树突时，攀爬纤维（CF）突触优先招募。与突触募集同时，细胞内分布从弥漫性细胞质转变为主要的细胞表面分布。在成人pc中，CF突触相关的积累是模糊的。相反，在PC树突表面三分之二的分子层上发现了显著的高表达，在这些分子层中，星状细胞驻留并投射轴突来支配PC树突。因此，pc中的体树突分布受特定输入或输入区域的调节。在发育过程中，KCC2向CF突触的定时募集将通过传入的BAs增强抑制性gaba能作用，促进周围PC神经中CF - to - BA的转换。在成年期，在PC树突星状细胞靶向区域丰富的KCC2表达可能有助于维持细胞内Cl -稳态和GABAA受体介导的中间神经元持续活动反应的极性。
Postnatal expression of the type 2 K+–Cl− cotransporter (KCC2) in neurons lowers the Cl− equilibrium potential to values that are more negative than the resting potential, thereby converting the action of Cl−‐permeable GABAA and glycine receptors from excitatory to inhibitory. In the present study, we investigated the spatiotemporal expression of KCC2 in mouse cerebella, particularly focusing on Purkinje cells (PCs). First, we confirmed the fundamental expression profiles of KCC2 in the cerebellum, i.e. neuron‐specific expression, somatodendritic distribution, and postnatal upregulation. We also found preferential recruitment to climbing fiber (CF) synapses during the second and third postnatal weeks, when perisomatic innervation in PCs switches from CFs to basket cell axons (BAs) and also when single winner CFs translocate from somata to dendrites. In parallel with this synaptic recruitment, the intracellular distribution shifted from a diffuse cytoplasmic to a predominantly cell surface pattern. In adult PCs, CF synapse‐associated accumulation was obscured. Instead, significantly high expression was noted on the surface of PC dendrites in the superficial two‐thirds of the molecular layer, in which stellate cells reside and project axons to innervate PC dendrites. Thus, the somatodendritic distribution in PCs is regulated in relation to particular inputs or input zones. During development, timed recruitment of KCC2 to CF synapses will augment inhibitory GABAergic actions by incoming BAs, promoting the CF‐to‐BA switchover in perisomatic PC innervation. In adulthood, enriched KCC2 expression at the stellate cell‐targeting territory of PC dendrites might help in maintaining intracellular Cl− homeostasis and the polarity of GABAA receptor‐mediated responses upon sustained activity of this interneuron.