Nitric oxide signaling modulates synaptic inhibition in the superior paraolivary nucleus (SPN) via cGMP-dependent suppression of KCC2.
Nitric oxide signaling modulates synaptic inhibition in the superior paraolivary nucleus (SPN) via cGMP-dependent suppression of KCC2.
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DOI：
10.3389/fncir.2014.00065
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发表时间：
2014
影响因子：
3.5
通讯作者：
Kopp-Scheinpflug C
中科院分区：
文献类型：
--
作者：
Yassin L;Radtke-Schuller S;Asraf H;Grothe B;Hershfinkel M;Forsythe ID;Kopp-Scheinpflug C
甘氨酸能抑制在听觉脑干回路中起着重要作用，听觉脑干回路参与声音定位和时间动作电位放电模式的编码。这种抑制的调制有可能微调这些网络中的信息处理。在这里，我们表明，一氧化氮（NO）信号在听觉脑干（其中活动依赖性产生的NO记录）调制的抑制强度，通过改变氯平衡电位。最近的证据表明，大的抑制性突触后电流（IPSC）的上级旁橄榄核（SPN）的神经元增强非常低的细胞内氯离子浓度，产生的神经元氯化钾共转运蛋白（KCC 2）中表达的突触后神经元。我们的数据表明，调制NO引起的IPSC逆转电位的15 mV的去极化移位，减少在SPN神经元的抑制强度，而不改变动作电位放电的阈值。通过靶神经元中KCC2功效的cGMP依赖性变化来调节抑制强度，提供了用于快速控制抑制驱动的突触后机制，而不改变传入尖峰串的定时或模式。因此，这种NO介导的KCC2抑制可以调节一个靶核（SPN）中的抑制，而不影响其他靶核（MSO，LSO）的抑制强度，即使它们各自接收来自相同传入核（来自斜方体内侧核的投射，MNTB）的侧支。
Glycinergic inhibition plays a central role in the auditory brainstem circuitries involved in sound localization and in the encoding of temporal action potential firing patterns. Modulation of this inhibition has the potential to fine-tune information processing in these networks. Here we show that nitric oxide (NO) signaling in the auditory brainstem (where activity-dependent generation of NO is documented) modulates the strength of inhibition by changing the chloride equilibrium potential. Recent evidence demonstrates that large inhibitory postsynaptic currents (IPSCs) in neurons of the superior paraolivary nucleus (SPN) are enhanced by a very low intracellular chloride concentration, generated by the neuronal potassium chloride co-transporter (KCC2) expressed in the postsynaptic neurons. Our data show that modulation by NO caused a 15 mV depolarizing shift of the IPSC reversal potential, reducing the strength of inhibition in SPN neurons, without changing the threshold for action potential firing. Regulating inhibitory strength, through cGMP-dependent changes in the efficacy of KCC2 in the target neuron provides a postsynaptic mechanism for rapidly controlling the inhibitory drive, without altering the timing or pattern of the afferent spike train. Therefore, this NO-mediated suppression of KCC2 can modulate inhibition in one target nucleus (SPN), without influencing inhibitory strength of other target nuclei (MSO, LSO) even though they are each receiving collaterals from the same afferent nucleus (a projection from the medial nucleus of the trapezoid body, MNTB).
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影响因子：
5.3
作者：
Chamma I;Chevy Q;Poncer JC;Lévi S
通讯作者：
Lévi S
影响因子：
5.1
作者：
Cherubini, Enrico;Griguoli, Marilena;Lagostena, Laura
通讯作者：
Lagostena, Laura
影响因子：
5.5
作者：
Fischl, Matthew J.;Combs, T. Dalton;Burger, R. Michael
通讯作者：
Burger, R. Michael
通过MZNR/GPR39受体对KCC2活性的上调。
DOI：
10.1523/jneurosci.2205-11.2011
发表时间：
2011-09-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chorin E;Vinograd O;Fleidervish I;Gilad D;Herrmann S;Sekler I;Aizenman E;Hershfinkel M
通讯作者：
Hershfinkel M
影响因子：
3.3
作者：
Coote, E. J.;Rees, A.
通讯作者：
Rees, A.