Turning off of GluN2B subunits and turning on of CICR in hippocampal LTD induction after developmental GluN2 subunit switch.
Turning off of GluN2B subunits and turning on of CICR in hippocampal LTD induction after developmental GluN2 subunit switch.
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发育性 GluN2 亚基转换后，海马 LTD 诱导中 GluN2B 亚基的关闭和 CICR 的开启。
DOI：
10.1002/hipo.22435
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发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
Hiroki Yasuda and Hideyuki Mukai
中科院分区：
文献类型：
--
作者：
Hikaru Sakamoto;Makito Hirano;Makoto Samukawa;Shuichi Ueno;Shuniji Maekura;Harutoshi Fujimura;Motoi Kuwahara;Yukihiro Hamada;Chiharu Isono;KeikoTanaka;Susumu Kusunoki;Yusaku Nakamura.;古本有香 斎藤祐見子;Hiroki Yasuda and Hideyuki Mukai
NMDA受体（NMDAR）对于诱导突触可塑性至关重要，突触可塑性介导发育期间神经回路的活动依赖性细化。NMDAR的GluN 2 B亚基在未成熟海马体中的突触处丰富，并且在出生后第二周（GluN 2亚基转换的关键时期），在酪蛋白激酶2活性的帮助下开始被GluN 2 A亚基取代（Sanz-Clemente等人（2000）Neuron 67：984-996）。然而，GluN 2B亚基在海马在这一关键时期的生理作用尚未阐明。在这里，我们报告说，GluN 2B亚基介导诱导海马CA 1区的长期抑郁症（LTD），直到这一时期。艾芬地尔和Ro 25 - 6981是含有GluN 2B亚基的NMDAR的选择性抑制剂，可阻断出生后第11-14天（P11-14）大鼠海马切片中的LTD，但在P18-22海马中则不然。P14后几天，突触NMDAR电流变得比P11-14时窄，通过NMDAR的钙内流必须减少。我们发现，钙诱导的钙释放（CICR）通过兰尼碱受体开始支持诱导NMDAR依赖性LTD在P18-22。细胞内应用毒胡萝卜素和ryanodine（分别是内部储存和ryanodine受体上的Ca 2 +-ATP泵抑制剂），在P11-14时完全不影响海马中的LTD，但在P18-22海马中完全阻断LTD。因此，通过具有GluN 2B亚基的NMDAR的钙内流足以在P11-14诱导LTD，之后CICR补偿LTD诱导期间钙内流的减少。© 2015威利期刊公司.
NMDA receptors (NMDARs) are essential for the induction of synaptic plasticity that mediates activity‐dependent refinement of neural circuits during development. GluN2B subunits of NMDARs are abundant at synapses in the immature hippocampus and begin to be replaced by GluN2A subunits with the help of casein kinase 2 activity in the second postnatal week, the critical period for the GluN2 subunit switch (Sanz‐Clemente et al. (2000) Neuron 67:984–996). However, the physiological role of GluN2B subunits in the hippocampus during this critical period has not been elucidated. Here, we report that GluN2B subunits mediate the induction of long‐term depression (LTD) in the CA1 region of the hippocampus only until this period. Ifenprodil and Ro25‐6981, selective inhibitors of NMDARs containing GluN2B subunits, blocked LTD in postnatal Day 11–14 (P11–14) rat hippocampal slices but not in P18–22 hippocampus. Just a few days after P14, synaptic NMDAR currents became narrower than those at P11–14, and calcium influx through NMDARs must be reduced. We found that calcium‐induced calcium release (CICR) through ryanodine receptors starts to support the induction of NMDAR‐dependent LTD at P18–22. Intracellular application of thapsigargin and ryanodine, inhibitors of Ca2+‐ATP pumps on internal stores and ryanodine receptors, respectively, did not at all affect LTD in the hippocampus at P11–14 but completely blocked LTD in the P18–22 hippocampus. Therefore, calcium influx through NMDAR with GluN2B subunits is sufficient to induce LTD at P11–14, after which CICR compensates for the decrease in calcium influx during LTD induction. © 2015 Wiley Periodicals, Inc.