Developmental Cajal-Retzius cell death contributes to the maturation of layer 1 cortical inhibition and somatosensory processing

• Published in: Nature communications 2024-08, Vol.15 (1), p.6501-15, Article 6501
• Main Authors: Damilou, Angeliki, Cai, Linbi, Argunşah, Ali Özgür, Han, Shuting, Kanatouris, George, Karatsoli, Maria, Hanley, Olivia, Gesuita, Lorenzo, Kollmorgen, Sepp, Helmchen, Fritjof, Karayannis, Theofanis
• Format: Article
• Language: English
• Subjects: 14/19; 14/63; 631/378/2571; 631/378/2629; 64/60; 9/30; 9/74; Animals; Apoptosis; Brain; Cell Death; Cerebral cortex; Circuits; Excitability; Female; GABAergic Neurons - metabolism; GABAergic Neurons - physiology; Genetics; Humanities and Social Sciences; Male; Maturation; Mice; Mice, Inbred C57BL; Mortality; multidisciplinary; Neocortex; Neocortex - cytology; Neocortex - physiology; Neural Inhibition - physiology; Neural networks; Neurons - metabolism; Neurons - physiology; Population genetics; Population studies; Pyramidal cells; Pyramidal Cells - metabolism; Pyramidal Cells - physiology; Science; Science (multidisciplinary); Somatosensory Cortex - cytology; Somatosensory Cortex - physiology; Vibrissae - physiology; γ-Aminobutyric acid
• ISSN: 2041-1723; 2041-1723
• 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. The role of apoptosis in the maturation of brain circuitry is not well understood. Here the authors show that the apoptosis of cortical layer 1 Cajal-Retzius cells regulates the maturation of the inhibitory circuit and somatosensory processing