Taurine depletion during fetal and postnatal development blunts firing responses of neocortical layer II/III pyramidal neurons.
Taurine depletion during fetal and postnatal development blunts firing responses of neocortical layer II/III pyramidal neurons.
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DOI：
10.3389/fnmol.2022.806798
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发表时间：
2022
影响因子：
4.8
通讯作者：
Fukuda, Atsuo
中科院分区：
文献类型：
--
作者：
Hosoi, Yasushi;Akita, Tenpei;Watanabe, Miho;Ito, Takashi;Miyajima, Hiroaki;Fukuda, Atsuo
胎儿和婴儿的大脑富含母体来源的牛磺酸。我们之前证明，牛磺酸作用可调节啮齿动物胎儿新皮质发育中的阳离子-氯化物协同转运蛋白活性以及锥体神经元祖细胞的分化和径向迁移。在这里，我们使用全细胞膜片钳技术检查了牛磺酸转运蛋白 Slc6a6 敲除引起的胎儿和婴儿牛磺酸消耗对出生后 3 周小鼠体感皮层 II/III 层锥体神经元放电特性的影响。基因敲除小鼠和野生型同窝小鼠的神经元在静息条件下的膜兴奋性相似。然而，在中等电流注入期间重复尖峰放电的频率明显较低，并且敲除神经元的尖峰间期期间的膜电压水平也较低。当注入强电流时，由于野生型神经元中电压门控Na+通道的失活，重复放电很快被消除，敲除神经元中的放电持续时间比野生型神经元长得多。这是由于敲除神经元中尖峰间期的膜电压水平低得多，从而促进了电压门控 Na+ 通道从失活中更大程度的恢复。因此，锥体神经元中牛磺酸的消耗通过增加重复放电的稳定性来减弱神经元对外部刺激的反应，这可能是由峰间间隔期间膜 K+ 电导的更大增加介导的。
Fetal and infant brains are rich in maternally derived taurine. We previously demonstrated that taurine action regulates the cation-chloride cotransporter activity and the differentiation and radial migration of pyramidal neuron progenitors in the developing neocortex of rodent fetuses. Here we examined the effects of fetal and infantile taurine depletion caused by knockout of the taurine transporter Slc6a6 on firing properties of layer II/III pyramidal neurons in the mouse somatosensory cortex at 3 weeks of postnatal age, using the whole-cell patch-clamp technique. The membrane excitability under resting conditions was similar between the neurons in knockout mice and those in wildtype littermates. However, the frequency of repetitive spike firing during moderate current injection was significantly lower, along with lower membrane voltage levels during interspike intervals in knockout neurons. When strong currents were injected, by which repetitive firing was rapidly abolished due to inactivation of voltage-gated Na+ channels in wildtype neurons, the firing in knockout neurons lasted for a much longer period than in wildtype neurons. This was due to much lower membrane voltage levels during interspike intervals in knockout neurons, promoting greater recovery of voltage-gated Na+ channels from inactivation. Thus, taurine depletion in pyramidal neurons blunted neuronal responses to external stimuli through increasing the stability of repetitive firing, presumably mediated by larger increases in membrane K+ conductance during interspike intervals.
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