Department of Psychiatry, University of Geneva Medical School, Geneva, Switzerland.
Department of Basic Neurosciences, University of Geneva Medical School, Geneva, Switzerland.
Int J Dev Neurosci. 2022 May;82(3):277-285. doi: 10.1002/jdn.10175. Epub 2022 Mar 11.
Alterations in the generation, migration and integration of different subtypes of neurons in the medial prefrontal cortex (mPFC) microcircuit could play an important role in vulnerability to schizophrenia. Using in vivo cell-type specific manipulation of pyramidal neurons (PNs) progenitors, we aim to investigate the role of the schizophrenia risk-gene DiGeorge Critical Region 2 (Dgcr2) on cortical circuit formation in the mPFC of developing mice. This report describes how Dgcr2 knock down in upper-layer PNs impacts the functional maturation of PNs and interneurons (INs) in the mPFC. First, we demonstrate that Dgcr2 knock-down disrupts laminar positioning, dendritic morphology and excitatory activity of upper-layer PNs. Interestingly, inhibitory activity is also modified in Dgcr2 knock-down PNs, suggesting a broader microcircuit alteration involving interneurons. Further analyses show that the histological maturation of parvalbumin (PV) INs is not dramatically impaired, thus implying that other INs subtypes might be at play in the reported microcircuit alteration. Overall, this study unravels how local functional deficits of the early postnatal development of the mPFC can be induced by Dgcr2 knock-down in PNs.
内侧前额叶皮层（mPFC）微电路中不同亚型神经元的产生、迁移和整合的改变可能在精神分裂症易感性中起重要作用。通过对锥体神经元（PNs）祖细胞进行体内细胞类型特异性操作，我们旨在研究精神分裂症风险基因 DiGeorge 关键区域 2（Dgcr2）在发育中小鼠 mPFC 皮质回路形成中的作用。本报告描述了 Dgcr2 敲低在上层 PN 中如何影响 mPFC 中 PN 和中间神经元（INs）的功能成熟。首先，我们证明 Dgcr2 敲低会破坏上层 PN 的层定位、树突形态和兴奋性活动。有趣的是，抑制性活动也在 Dgcr2 敲低 PN 中发生改变，这表明涉及中间神经元的更广泛的微电路改变。进一步的分析表明，PV INs 的组织成熟并未受到明显损害，因此暗示在报道的微电路改变中可能涉及其他 INs 亚型。总的来说，这项研究揭示了 Dgcr2 在 PN 中的敲低如何诱导 mPFC 早期出生后发育的局部功能缺陷。
