A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior.
A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior.
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DOI：
10.1016/j.celrep.2016.12.002
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发表时间：
2016-12-20
期刊：
影响因子：
8.8
通讯作者：
Elliott DJ
中科院分区：
文献类型：
--
作者：
Ehrmann I;Gazzara MR;Pagliarini V;Dalgliesh C;Kheirollahi-Chadegani M;Xu Y;Cesari E;Danilenko M;Maclennan M;Lowdon K;Vogel T;Keskivali-Bond P;Wells S;Cater H;Fort P;Santibanez-Koref M;Middei S;Sette C;Clowry GJ;Barash Y;Cunningham MO;Elliott DJ
大脑由数万亿个突触连接组成，这些突触连接共同形成正常大脑功能和行为所需的神经网络。SLM 2是RNA结合蛋白保守家族的成员，包括Sam 68和SLM 1，其控制Neurexin 1 -3前mRNA的剪接。SLM 2是否影响神经网络活动尚不清楚。在这里，我们发现SLM 2水平是通过稳态反馈控制途径维持的，该途径早于SLM 2和Sam 68的分歧。SLM 2还控制Tomosyn 2、LysoPLD/ATX、Dgkb、Kif 21 a和Cask的剪接，其中每一个对突触功能都很重要。皮质神经网络活动依赖于SLM 2表达的锥体神经元和中间神经元之间的突触连接在SLM 2基因敲除小鼠中减少。此外，这些小鼠焦虑，识别新物体的能力下降。我们的数据揭示了SLM 2稳态自动调节控制脑网络活动和行为的途径。SLM 2剪接靶点在海马内受到空间控制RNA-seq揭示了SLM 2反馈控制和突触蛋白剪接靶点SLM 2的丢失抑制了海马γ振荡的模式SLM 2的丢失改变了依赖于这些神经网络的小鼠行为SLM 2是一种RNA结合蛋白，保守了25.5亿年。Ehrmann等人确定一种控制整个大脑中SLM 2表达的稳态反馈途径。SLM 2蛋白的缺失导致神经网络活动的缺陷并改变小鼠行为。
The brain is made up of trillions of synaptic connections that together form neural networks needed for normal brain function and behavior. SLM2 is a member of a conserved family of RNA binding proteins, including Sam68 and SLM1, that control splicing of Neurexin1-3 pre-mRNAs. Whether SLM2 affects neural network activity is unknown. Here, we find that SLM2 levels are maintained by a homeostatic feedback control pathway that predates the divergence of SLM2 and Sam68. SLM2 also controls the splicing of Tomosyn2, LysoPLD/ATX, Dgkb, Kif21a, and Cask, each of which are important for synapse function. Cortical neural network activity dependent on synaptic connections between SLM2-expressing-pyramidal neurons and interneurons is decreased in Slm2-null mice. Additionally, these mice are anxious and have a decreased ability to recognize novel objects. Our data reveal a pathway of SLM2 homeostatic auto-regulation controlling brain network activity and behavior. SLM2 splicing targets are spatially controlled within the hippocampus RNA-seq reveals SLM2 feedback control and synaptic protein splicing targets Loss of SLM2 dampens patterns of hippocampal γ oscillations Loss of SLM2 changes mouse behavior that depends on these neural networks SLM2 is an RNA binding protein conserved for ∼550 million years. Ehrmann et al. identify a homeostatic feedback pathway that controls SLM2 expression across the brain. Loss of SLM2 protein causes defects in neural network activity and changes mouse behavior.
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影响因子：
25
作者：
Aoto, Jason;Foeldy, Csaba;Ilcus, Silviana Maria Ciurea;Tabuchi, Katsuhiko;Suedhof, Thomas C.
通讯作者：
Suedhof, Thomas C.
影响因子：
5.3
作者：
Gauthier J;Siddiqui TJ;Huashan P;Yokomaku D;Hamdan FF;Champagne N;Lapointe M;Spiegelman D;Noreau A;Lafrenière RG;Fathalli F;Joober R;Krebs MO;DeLisi LE;Mottron L;Fombonne E;Michaud JL;Drapeau P;Carbonetto S;Craig AM;Rouleau GA
通讯作者：
Rouleau GA
ATX 在发育中大脑中的非细胞自主和非催化活性。
影响因子：
4.3
作者：
Greenman R;Gorelik A;Sapir T;Baumgart J;Zamor V;Segal-Salto M;Levin-Zaidman S;Aidinis V;Aoki J;Nitsch R;Vogt J;Reiner O
通讯作者：
Reiner O
影响因子：
16.2
作者：
Buzsáki G;Logothetis N;Singer W
通讯作者：
Singer W
影响因子：
3
作者：
Basar-Eroglu, Canan;Brand, Andreas;Schmiedt, Christina
通讯作者：
Schmiedt, Christina