Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK.
Department of Physiology and Department of Neurology, School of Medicine, University of California San Francisco, San Francisco, CA, USA.
Cell Rep. 2022 Jul 5;40(1):111037. doi: 10.1016/j.celrep.2022.111037.
One key factor underlying the functional balance of cortical networks is the ratio of excitatory and inhibitory neurons. The mechanisms controlling the ultimate number of interneurons are beginning to be elucidated, but to what extent similar principles govern the survival of the large diversity of cortical inhibitory cells remains to be investigated. Here, we investigate the mechanisms regulating developmental cell death in neurogliaform cells, bipolar cells, and basket cells, the three main populations of interneurons originating from the caudal ganglionic eminence and the preoptic region. We found that all three subclasses of interneurons undergo activity-dependent programmed cell death. However, while neurogliaform cells and basket cells require glutamatergic transmission to survive, the final number of bipolar cells is instead modulated by serotonergic signaling. Together, our results demonstrate that input-specific modulation of neuronal activity controls the survival of cortical interneurons during the critical period of programmed cell death.
皮质网络功能平衡的一个关键因素是兴奋性和抑制性神经元的比例。控制中间神经元最终数量的机制开始被阐明,但类似的原则在多大程度上控制着皮质抑制性细胞的多样性的存活仍有待研究。在这里,我们研究了调节神经胶质形态细胞、双极细胞和篮状细胞发育性细胞死亡的机制,这三种中间神经元主要来源于尾状神经节隆起和视前区。我们发现,这三种中间神经元亚类都经历了活性依赖的程序性细胞死亡。然而,虽然神经胶质形态细胞和篮状细胞需要谷氨酸能传递才能存活,但双极细胞的最终数量则是由 5-羟色胺信号调制的。总之,我们的研究结果表明,神经元活动的输入特异性调节控制了程序性细胞死亡关键期皮质中间神经元的存活。