Disruption of Kcc2-dependent inhibition of olfactory bulb output neurons suggests its importance in odour discrimination.
Disruption of Kcc2-dependent inhibition of olfactory bulb output neurons suggests its importance in odour discrimination.
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DOI：
10.1038/ncomms12043
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发表时间：
2016-07-08
影响因子：
16.6
通讯作者：
Jentsch TJ
中科院分区：
文献类型：
--
作者：
Gödde K;Gschwend O;Puchkov D;Pfeffer CK;Carleton A;Jentsch TJ
嗅球是嗅觉信息传递的第一个中继站，其突触抑制被认为在气味辨别中起重要作用。我们干扰GABA能抑制二尖瓣和簇状细胞（M/T细胞），OB的主要神经元，通过破坏他们的钾-氯协同转运蛋白2（Kcc 2）。大约70%的小鼠在3周左右死亡，但存活的小鼠看起来正常。在这些小鼠中，细胞内Cl−浓度的增加几乎消除了GABA诱导的二尖瓣细胞（MC）超极化，并意外地增加了MC上的体周突触数量。气味诱导的OB电活动的体内分析显示增加的M/T细胞放电率，改变呼吸周期中动作电位的相位，并破坏气味诱导的M/T细胞活动模式的分离。小鼠也表现出严重受损的能力，区分化学相似的气味或气味混合物。我们的工作表明，精确调谐GABA能抑制M/T细胞是至关重要的M/T细胞的尖峰模式分离需要区分密切相似的气味。 嗅球（OB）中的突触抑制被认为在气味处理中起作用。在这里，作者使用Pcdh 21驱动的Cre-line来破坏OB二尖瓣细胞中的KCC 2表达，并发现改变的突触连接沿着气味诱导的活动模式的破坏分离。
Synaptic inhibition in the olfactory bulb (OB), the first relay station of olfactory information, is believed to be important for odour discrimination. We interfered with GABAergic inhibition of mitral and tufted cells (M/T cells), the principal neurons of the OB, by disrupting their potassium-chloride cotransporter 2 (Kcc2). Roughly, 70% of mice died around 3 weeks, but surviving mice appeared normal. In these mice, the resulting increase in the intracellular Cl− concentration nearly abolished GABA-induced hyperpolarization of mitral cells (MCs) and unexpectedly increased the number of perisomatic synapses on MCs. In vivo analysis of odorant-induced OB electrical activity revealed increased M/T cell firing rate, altered phasing of action potentials in the breath cycle and disrupted separation of odour-induced M/T cell activity patterns. Mice also demonstrated a severely impaired ability to discriminate chemically similar odorants or odorant mixtures. Our work suggests that precisely tuned GABAergic inhibition onto M/T cells is crucial for M/T cell spike pattern separation needed to distinguish closely similar odours. Synaptic inhibition in the olfactory bulb (OB) is believed to play a role in odour processing. Here, the authors use a Pcdh21-driven Cre-line to disrupt KCC2 expression in OB mitral cells and find altered synaptic connectivity along with disrupted separation of odour-induced activity patterns.