Mahar Ian, MacIsaac Angus, Kim John Junghan, Qiang Calvin, Davoli Maria Antonietta, Turecki Gustavo, Mechawar Naguib
McGill Group for Suicide Studies, Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Québec, H4H 1R3, Canada.
Integrated Program in Neuroscience, McGill University, Montreal Neurological Institute, 3801 University Street, Montréal, QC H3A 2B4, Canada.
Sci Rep. 2016 Jul 29;6:30467. doi: 10.1038/srep30467.
Adult hippocampal neurogenesis is associated with learning and affective behavioural regulation. Its diverse functionality is segregated along the septotemporal axis from the dorsal to ventral hippocampus. However, features distinguishing immature neurons in these regions have yet to be characterized. Additionally, although we have shown that administration of the neurotrophic factor neuregulin-1 (NRG1) selectively increases proliferation and overall neurogenesis in the mouse ventral dentate gyrus (DG), likely through ErbB3, NRG1's effects on intermediate neurogenic stages in immature neurons are unknown. We examined whether NRG1 administration increases DG ErbB3 phosphorylation. We labeled adultborn cells using BrdU, then administered NRG1 to examine in vivo neurogenic effects on immature neurons with respect to cell survival, morphology, and synaptogenesis. We also characterized features of immature neurons along the septotemporal axis. We found that neurogenic effects of NRG1 are temporally and subregionally specific to proliferation in the ventral DG. Particular morphological features differentiate immature neurons in the dorsal and ventral DG, and cytogenesis differed between these regions. Finally, we identified synaptic heterogeneity surrounding the granule cell layer. These results indicate neurogenic involvement of NRG1-induced antidepressant-like behaviour is particularly associated with increased ventral DG cell proliferation, and identify novel distinctions between dorsal and ventral hippocampal neurogenic development.
成体海马神经发生与学习及情感行为调节相关。其多样的功能沿海马从背侧到腹侧的隔颞轴分离。然而，区分这些区域未成熟神经元的特征尚未得到描述。此外，尽管我们已经表明神经营养因子神经调节蛋白-1（NRG1）的给药选择性地增加了小鼠腹侧齿状回（DG）中的增殖和整体神经发生，可能是通过ErbB3，但NRG1对未成熟神经元中间神经发生阶段的影响尚不清楚。我们研究了NRG1给药是否会增加DG中ErbB3的磷酸化。我们用BrdU标记成年新生细胞，然后给予NRG1，以研究其在体内对未成熟神经元在细胞存活、形态和突触发生方面的神经发生作用。我们还描述了沿隔颞轴的未成熟神经元的特征。我们发现NRG1的神经发生作用在时间和区域上对腹侧DG中的增殖具有特异性。特定的形态特征区分了背侧和腹侧DG中的未成熟神经元，并且这些区域之间的细胞发生也有所不同。最后，我们确定了颗粒细胞层周围的突触异质性。这些结果表明，NRG1诱导的抗抑郁样行为的神经发生参与尤其与腹侧DG细胞增殖增加有关，并确定了背侧和腹侧海马神经发生发育之间的新差异。
