Transient developmental imbalance of cortical interneuron subtypes presages long-term changes in behavior.
Transient developmental imbalance of cortical interneuron subtypes presages long-term changes in behavior.
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DOI：
10.1016/j.celrep.2021.109249
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发表时间：
2021-06-15
期刊：
影响因子：
8.8
通讯作者：
Kessaris N
中科院分区：
文献类型：
--
作者：
Magno L;Asgarian Z;Pendolino V;Velona T;Mackintosh A;Lee F;Stryjewska A;Zimmer C;Guillemot F;Farrant M;Clark B;Kessaris N
皮层gaba能中间神经元在神经节突起大量生成，并在胚胎发生期间迁移到大脑皮层。在出生后的早期阶段，在神经元回路成熟过程中，皮层内的自主和活动依赖机制通过消除自然发生的神经元过剩来调节细胞数量。在这里，我们发现，当皮层中间神经元数量异常高时——由于胚胎发育过程中前体细胞增殖缺陷——额外的小白蛋白中间神经元在出生后小鼠皮层网络成熟的关键时期持续存在。即使细胞数量随后正常化，行为异常仍然存在于成年期。这表明及时清除多余的皮层中间神经元对于驱动成人行为的回路的正确功能成熟至关重要。过量的小白蛋白（PV）中间神经元整合到出生后早期的皮质中。过量的PV中间神经元通过pten依赖机制被消除。在异常的中间神经元过剩被清除后，行为异常仍会持续很长时间。Magno等人证明异常的小白蛋白中间神经元过剩在出生后皮层中持续存在，跨越皮层网络成熟的关键时期。细胞数量最终正常化，但行为异常仍然存在于成年期。
Cortical GABAergic interneurons are generated in large numbers in the ganglionic eminences and migrate into the cerebral cortex during embryogenesis. At early postnatal stages, during neuronal circuit maturation, autonomous and activity-dependent mechanisms operate within the cortex to adjust cell numbers by eliminating naturally occurring neuron excess. Here, we show that when cortical interneurons are generated in aberrantly high numbers—due to a defect in precursor cell proliferation during embryogenesis—extra parvalbumin interneurons persist in the postnatal mouse cortex during critical periods of cortical network maturation. Even though cell numbers are subsequently normalized, behavioral abnormalities remain in adulthood. This suggests that timely clearance of excess cortical interneurons is critical for correct functional maturation of circuits that drive adult behavior. CUX2 regulates cortical parvalbumin interneuron number generation in the MGE Excess parvalbumin (PV) interneuron integrates into the early postnatal cortex Excess PV interneuron is eliminated through PTEN-dependent mechanisms Behavioral abnormalities persist long after abnormal interneuron excess is cleared Cortical interneurons are generated in excess during embryogenesis, and numbers are trimmed soon after birth for optimal inhibition. Magno et al. demonstrate that aberrant parvalbumin interneuron excess persists in the postnatal cortex, spanning critical periods of cortical network maturation. Cell numbers are eventually normalized, but behavioral abnormalities remain in adulthood.
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影响因子：
5.7
作者：
Kessaris N;Magno L;Rubin AN;Oliveira MG
通讯作者：
Oliveira MG
错义突变热点识别神经发育障碍基因和功能域
影响因子：
25
作者：
Geisheker MR;Heymann G;Wang T;Coe BP;Turner TN;Stessman HAF;Hoekzema K;Kvarnung M;Shaw M;Friend K;Liebelt J;Barnett C;Thompson EM;Haan E;Guo H;Anderlid BM;Nordgren A;Lindstrand A;Vandeweyer G;Alberti A;Avola E;Vinci M;Giusto S;Pramparo T;Pierce K;Nalabolu S;Michaelson JJ;Sedlacek Z;Santen GWE;Peeters H;Hakonarson H;Courchesne E;Romano C;Kooy RF;Bernier RA;Nordenskjöld M;Gecz J;Xia K;Zweifel LS;Eichler EE
通讯作者：
Eichler EE
影响因子：
4.9
作者：
Gogolla, Nadine;LeBlanc, Jocelyn J.;Quast, Kathleen B.;Sudhof, Thomas C.;Fagiolini, Michela;Hensch, Takao K.
通讯作者：
Hensch, Takao K.
影响因子：
9.8
作者：
Harris KD;Hochgerner H;Skene NG;Magno L;Katona L;Bengtsson Gonzales C;Somogyi P;Kessaris N;Linnarsson S;Hjerling-Leffler J
通讯作者：
Hjerling-Leffler J
影响因子：
5.3
作者：
Dehorter N;Del Pino I
通讯作者：
Del Pino I