The Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
PLoS One. 2012;7(9):e41029. doi: 10.1371/journal.pone.0041029. Epub 2012 Sep 5.
The dentate gyrus is a neurogenic zone where neurons continue to be born throughout life, mature and integrate into the local circuitry. In adults, this generation of new neurons is thought to contribute to learning and memory formation. As newborn neurons mature, they undergo a developmental sequence in which different stages of development are marked by expression of different proteins. Doublecortin (DCX) is an early marker that is expressed in immature granule cells that are beginning migration and dendritic growth but is turned off before neurons reach maturity. In the present study, we use a mouse strain in which enhanced green fluorescent protein (EGFP) is expressed under the control of the DCX promoter. We show that these neurons have high input resistances and some cells can discharge trains of action potentials. In mature granule cells, action potentials are followed by a slow afterhyperpolarization that is absent in EGFP-positive neurons. EGFP-positive neurons had a lower spine density than mature neurons and stimulation of either the medial or lateral perforant pathway activated dual component glutamatergic synapses that had both AMPA and NMDA receptors. NMDA receptors present at these synapses had slow kinetics and were blocked by ifenprodil, indicative of high GluN2B subunit content. These results show that EGFP-positive neurons in the DCX-EGFP mice are functionally immature both in their firing properties and excitatory synapses.
齿状回是一个神经发生区,在整个生命过程中,神经元不断生成、成熟并整合到局部回路中。在成年人中,这些新神经元的产生被认为有助于学习和记忆的形成。随着新生神经元的成熟,它们经历了一个发育序列,在这个序列中,不同的发育阶段通过表达不同的蛋白质来标记。双皮质素 (DCX) 是一种早期标志物,在开始迁移和树突生长的不成熟颗粒细胞中表达,但在神经元成熟之前关闭。在本研究中,我们使用了一种在 DCX 启动子控制下表达增强型绿色荧光蛋白 (EGFP) 的小鼠品系。我们表明,这些神经元具有高输入电阻,并且一些细胞可以发射动作电位串。在成熟的颗粒细胞中,动作电位后紧接着是缓慢的后超极化,而在 EGFP 阳性神经元中则没有。EGFP 阳性神经元的棘突密度低于成熟神经元,刺激内侧或外侧穿通路径均可激活具有 AMPA 和 NMDA 受体的双成分谷氨酸能突触。这些突触中的 NMDA 受体具有缓慢的动力学,被ifenprodil 阻断,表明 GluN2B 亚基含量高。这些结果表明,DCX-EGFP 小鼠中的 EGFP 阳性神经元在其放电特性和兴奋性突触中均表现出功能不成熟。