Spatiotemporal SERT expression in cortical map development.

Spatiotemporal SERT expression in cortical map development.
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DOI:
10.1016/j.neuint.2016.05.010
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发表时间:
2016-09
影响因子:
4.2
通讯作者:
Sze JY
Sze JY
中科院分区:
医学3区
文献类型:
--
作者:
Chen X;Petit EI;Dobrenis K;Sze JY

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大脑皮层被组织成形态上不同的区域,这些区域提供了感知、认知和行为的生物框架。分析小鼠和人类皮层转录组揭示了时间特异性差异基因表达模块在不同的新皮层地区在皮层地图的建立。然而,时空基因表达的生物学作用在皮质图案和皮质地形基因表达的调节在很大程度上是未知的。在这里,我们的特点的时间和空间定义的表达5-羟色胺(5-HT)转运蛋白(SERT)在小鼠感觉地图的发展过程中的海马神经元。SERT在投射到感觉皮层的丘脑能神经元中以及在前额叶皮层(PFC)和海马(HPC)的锥体神经元中在奠定基本功能神经回路的时期瞬时表达。我们以前发现,在丘脑神经元中敲除SERT会阻断丘脑皮质轴突对5-HT的摄取,导致过度的5-HT信号传导损害感觉地图结构。相反,在这里,我们表明,选择性SERT敲除PFC和HPC神经元不扰乱感觉地图图案。这些数据表明,在特定的海马神经元的瞬时SERT表达提供了区域特定的指令皮质地图图案。因此,这种SERT功能的遗传和药理学操作可以阐明皮质特异性地图的基本遗传编程和时间特异性皮质地形基因表达在正常发育和精神障碍中的生物学作用。
The cerebral cortex is organized into morphologically distinct areas that provide biological frameworks underlying perception, cognition, and behavior. Profiling mouse and human cortical transcriptomes have revealed temporal-specific differential gene expression modules in distinct neocortical areas during cortical map establishment. However, the biological roles of spatiotemporal gene expression in cortical patterning and how cortical topographic gene expression is regulated are largely unknown. Here, we characterize temporal- and spatial-defined expression of serotonin (5-HT) transporter (SERT) in glutamatergic neurons during sensory map development in mice. SERT is transiently expressed in glutamatergic thalamic neurons projecting to sensory cortices and in pyramidal neurons in the prefrontal cortex (PFC) and hippocampus (HPC) during the period that lays down the basic functional neural circuits. We previously identified that knockout of SERT in the thalamic neurons blocks 5-HT uptake by their thalamocortical axons, resulting in excessive 5-HT signaling that impairs sensory map architecture. In contrast, here we show that selective SERT knockout in the PFC and HPC neurons does not perturb sensory map patterning. These data suggest that transient SERT expression in specific glutamatergic neurons provides area-specific instructions for cortical map patterning. Hence, genetic and pharmacological manipulations of this SERT function could illuminate the fundamental genetic programming of cortex-specific maps and biological roles of temporal-specific cortical topographic gene expression in normal development and mental disorders.