Developmentally regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome.
Developmentally regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome.
复制标题
Dravet综合征实验模型中发育调节的小白蛋白神经元间突触传递损伤。
DOI：
10.1016/j.celrep.2022.110580
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发表时间：
2022-03-29
期刊：
影响因子：
8.8
通讯作者：
Goldberg, Ethan M.
中科院分区：
文献类型：
--
作者：
Kaneko, Keisuke;Currin, Christopher B.;Goff, Kevin M.;Wengert, Eric R.;Somarowthu, Ala;Vogels, Tim P.;Goldberg, Ethan M.
Dravet综合征是一种神经发育障碍，其特征是由于SCN 1A致病性变异伴钠通道亚基Nav1.1功能丧失导致癫痫、智力残疾和猝死。来自年轻Scn 1a +/−小鼠的Nav1.1表达小清蛋白GABA能中间神经元（PV-IN）表现出动作电位产生受损。在两个时间点评估相同小鼠PV-IN功能的方法显示，在出生后第16-21天（P），所有Scn 1a +/−小鼠的棘波生成受损，无论是在P35之前死亡还是存活至P35，存活小鼠的P35正常化。然而，PV-IN突触传递在未存活的年轻Scn 1a +/−小鼠和≥ P35的Scn 1a +/−小鼠中功能障碍。建模证实，PV-IN轴突传播是更敏感的降低钠电导比穗代。这些结果表明Dravet综合征中的动态功能障碍：PV-IN尖峰产生和传播的组合异常驱动早期疾病严重程度，而突触传递的持续功能障碍促成慢性病理学。Dravet综合征是由SCN 1A变异引起的，伴有Nav1.1钠通道功能丧失。Kaneko等人使用“迷你切片”记录两个发育时间点。Scn 1a +/−小鼠中表达Nav1.1的PV中间神经元的棘波生成受损是短暂的，而PV中间神经元突触传递异常持续存在。
Dravet syndrome is a neurodevelopmental disorder characterized by epilepsy, intellectual disability, and sudden death due to pathogenic variants in SCN1A with loss of function of the sodium channel subunit Nav1.1. Nav1.1-expressing parvalbumin GABAergic interneurons (PV-INs) from young Scn1a+/− mice show impaired action potential generation. An approach assessing PV-IN function in the same mice at two time points shows impaired spike generation in all Scn1a+/− mice at postnatal days (P) 16–21, whether deceased prior or surviving to P35, with normalization by P35 in surviving mice. However, PV-IN synaptic transmission is dysfunctional in young Scn1a+/− mice that did not survive and in Scn1a+/− mice ≥ P35. Modeling confirms that PV-IN axonal propagation is more sensitive to decreased sodium conductance than spike generation. These results demonstrate dynamic dysfunction in Dravet syndrome: combined abnormalities of PV-IN spike generation and propagation drives early disease severity, while ongoing dysfunction of synaptic transmission contributes to chronic pathology. Dravet syndrome is caused by variants in SCN1A with loss of function of Nav1.1 sodium channels. Kaneko et al. use the “mini-slice” to record at two developmental time points. Impaired spike generation of Nav1.1-expressing PV interneurons in Scn1a+/− mice is transient, while abnormalities of PV interneuron synaptic transmission persist.
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影响因子：
5.3
作者：
Dutton SBB;Dutt K;Papale LA;Helmers S;Goldin AL;Escayg A
通讯作者：
Escayg A
影响因子：
3.7
作者：
Grubb MS;Burrone J
通讯作者：
Burrone J
影响因子：
16.6
作者：
Espinoza C;Guzman SJ;Zhang X;Jonas P
通讯作者：
Jonas P
DOI：
10.1523/jneurosci.4064-11.2011
发表时间：
2011-11-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Grubb MS;Shu Y;Kuba H;Rasband MN;Wimmer VC;Bender KJ
通讯作者：
Bender KJ
影响因子：
5.5
作者：
Boudkkazi, Sami;Fronzaroli-Molinieres, Laure;Debanne, Dominique
通讯作者：
Debanne, Dominique