Stroke Accelerates and Uncouples Intrinsic and Synaptic Excitability Maturation of Mouse Hippocampal DCX+ Adult-Born Granule Cells
Stroke Accelerates and Uncouples Intrinsic and Synaptic Excitability Maturation of Mouse Hippocampal DCX+ Adult-Born Granule Cells
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DOI：
10.1523/jneurosci.3303-17.2018
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发表时间：
2019-02-27
影响因子：
5.3
通讯作者：
Kunze, Albrecht
中科院分区：
文献类型：
--
作者：
Ceanga, Mihai;Keiner, Silke;Kunze, Albrecht
中风有力地刺激成人在海马齿状回的神经发生。目前尚不清楚这一过程是否会导致有益的或不适应的影响，但形态和行为研究已经报道了中风后神经发生的异常和海马区依赖记忆的损害。然而，成体出生的颗粒细胞(ABGC)在缺血后的内在功能和网络整合尚不清楚。应用膜片钳电生理学方法，对卒中或假手术后2周的DCX/DsRed转基因小鼠双皮质醇阳性ABGCs和DCX齿状回颗粒细胞进行检测。卒中后ABGC的发育状态、内在兴奋性和突触兴奋性加快，而树突状细胞形态无异常。回归分析揭示了内在兴奋性和网络兴奋性的分离发展，导致年轻的、内在的过度兴奋的ABGC接受不成比例的大的谷氨酸能输入。海马区ABGC亚群的这种异常功能成熟可能是导致海马区功能缺陷和中风后癫痫易感性增加的原因之一。
Stroke robustly stimulates adult neurogenesis in the hippocampal dentate gyrus. It is currently unknown whether this process induces beneficial or maladaptive effects, but morphological and behavioral studies have reported aberrant neurogenesis and impaired hippocampal-dependent memory following stroke. However, the intrinsic function and network incorporation of adult-born granule cells (ABGCs) after ischemia is unclear. Using patch-clamp electrophysiology, we evaluated doublecortin-positive (DCX) ABGCs as well as DCX dentate gyms granule cells 2 weeks after a stroke or sham operation in DCX/DsRed transgenic mice of either sex. The developmental status, intrinsic excitability, and synaptic excitability of ABGCs were accelerated following stroke, while dendritic morphology was not aberrant. Regression analysis revealed uncoupled development of intrinsic and network excitability, resulting in young, intrinsically hyperexcitable ABGCs receiving disproportionately large glutamatergic inputs. This aberrant functional maturation in the subgroup of ABGCs in the hippocampus may contribute to defective hippocampal function and increased seizure susceptibility following stroke.