Damilou Angeliki, Cai Linbi, Argunşah Ali Özgür, Han Shuting, Kanatouris George, Karatsoli Maria, Hanley Olivia, Gesuita Lorenzo, Kollmorgen Sepp, Helmchen Fritjof, Karayannis Theofanis
Laboratory of Neural Circuit Assembly, Brain Research Institute (HiFo), University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
Adaptive Brain Circuits in Development and Learning (AdaBD), University Research Priority Program (URPP), University of Zürich, Zürich, 8057, Switzerland.
Nat Commun. 2024 Aug 1;15(1):6501. doi: 10.1038/s41467-024-50658-6.
The role of developmental cell death in the formation of brain circuits is not well understood. Cajal-Retzius cells constitute a major transient neuronal population in the mammalian neocortex, which largely disappears at the time of postnatal somatosensory maturation. In this study, we used mouse genetics, anatomical, functional, and behavioral approaches to explore the impact of the early postnatal death of Cajal-Retzius cells in the maturation of the cortical circuit. We find that before their death, Cajal-Retzius cells mainly receive inputs from layer 1 neurons, which can only develop their mature connectivity onto layer 2/3 pyramidal cells after Cajal-Retzius cells disappear. This developmental connectivity progression from layer 1 GABAergic to layer 2/3 pyramidal cells regulates sensory-driven inhibition within, and more so, across cortical columns. Here we show that Cajal-Retzius cell death prevention leads to layer 2/3 hyper-excitability, delayed learning and reduced performance in a multi-whisker-dependent texture discrimination task.
发育性细胞死亡在脑回路形成中的作用尚未得到充分理解。卡哈尔-雷茨乌斯细胞是哺乳动物新皮层中的主要短暂神经元群体，在出生后体感成熟时基本消失。在本研究中，我们使用小鼠遗传学、解剖学、功能学和行为学方法，来探究出生后早期卡哈尔-雷茨乌斯细胞死亡对皮质回路成熟的影响。我们发现，在死亡之前，卡哈尔-雷茨乌斯细胞主要接收来自第1层神经元的输入，只有在卡哈尔-雷茨乌斯细胞消失后，第1层神经元才能在第2/3层锥体细胞上形成成熟的连接。这种从第1层γ-氨基丁酸能神经元到第2/3层锥体细胞的发育性连接进展，调节了皮质柱内以及更多跨皮质柱的感觉驱动抑制。在这里我们表明，预防卡哈尔-雷茨乌斯细胞死亡会导致第2/3层过度兴奋、学习延迟，并在多须依赖的纹理辨别任务中表现下降。
