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单个转录调节因子 ID2 对成年海马苔藓纤维系统的反复重塑。

Recurrent rewiring of the adult hippocampal mossy fiber system by a single transcriptional regulator, Id2.

机构信息

Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Science, University of Zürich, Zürich, 8057, Switzerland.

Szentágothai Research Center, Department of Physiology, Medical School, University of Pécs, Pécs, 7624, Hungary.

出版信息

Proc Natl Acad Sci U S A. 2021 Oct 5;118(40). doi: 10.1073/pnas.2108239118.

DOI:10.1073/pnas.2108239118
PMID:34599103
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8501755/
Abstract

Circuit formation in the central nervous system has been historically studied during development, after which cell-autonomous and nonautonomous wiring factors inactivate. In principle, balanced reactivation of such factors could enable further wiring in adults, but their relative contributions may be circuit dependent and are largely unknown. Here, we investigated hippocampal mossy fiber sprouting to gain insight into wiring mechanisms in mature circuits. We found that sole ectopic expression of Id2 in granule cells is capable of driving mossy fiber sprouting in healthy adult mouse and rat. Mice with the new mossy fiber circuit solved spatial problems equally well as controls but appeared to rely on local rather than global spatial cues. Our results demonstrate reprogrammed connectivity in mature neurons by one defined factor and an assembly of a new synaptic circuit in adult brain.

摘要

中枢神经系统的回路形成在历史上是在发育过程中进行研究的,之后细胞自主和非自主的布线因素失活。原则上,这些因素的平衡再激活可以使成年人进一步布线,但它们的相对贡献可能取决于回路,而且在很大程度上是未知的。在这里,我们研究了海马苔藓纤维的发芽,以深入了解成熟回路的布线机制。我们发现,仅仅在颗粒细胞中异位表达 Id2 就能够驱动健康成年小鼠和大鼠的苔藓纤维发芽。具有新苔藓纤维回路的小鼠在解决空间问题方面与对照组一样好,但似乎依赖于局部而不是全局的空间线索。我们的结果证明了一个定义明确的因素可以重新编程成熟神经元的连接,并在成年大脑中组装一个新的突触回路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/2af474183f1f/pnas.2108239118fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/a47eabf7a5a7/pnas.2108239118fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/1a077efe043f/pnas.2108239118fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/897d49f673bf/pnas.2108239118fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/ba863ccb3201/pnas.2108239118fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/f79b6b80611c/pnas.2108239118fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/2fe3a78a7cc6/pnas.2108239118fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/2af474183f1f/pnas.2108239118fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/a47eabf7a5a7/pnas.2108239118fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/1a077efe043f/pnas.2108239118fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/897d49f673bf/pnas.2108239118fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/ba863ccb3201/pnas.2108239118fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/f79b6b80611c/pnas.2108239118fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/2fe3a78a7cc6/pnas.2108239118fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e56/8501755/2af474183f1f/pnas.2108239118fig07.jpg

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