Department of Neurology and F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA; email:
Stanley Center, Broad Institute, Cambridge, Massachusetts 02142, USA.
Annu Rev Neurosci. 2019 Jul 8;42:107-127. doi: 10.1146/annurev-neuro-070918-050306.
Maturation of neuronal circuits requires selective elimination of synaptic connections. Although neuron-intrinsic mechanisms are important in this process, it is increasingly recognized that glial cells also play a critical role. Without proper functioning of these cells, the number, morphology, and function of synaptic contacts are profoundly altered, resulting in abnormal connectivity and behavioral abnormalities. In addition to their role in synaptic refinement, glial cells have also been implicated in pathological synapse loss and dysfunction following injury or nervous system degeneration in adults. Although mechanisms regulating glia-mediated synaptic elimination are still being uncovered, it is clear this complex process involves many cues that promote and inhibit the removal of specific synaptic connections. Gaining a greater understanding of these signals and the contribution of different cell types will not only provide insight into this critical biological event but also be instrumental in advancing knowledge of brain development and neural disease.
神经元回路的成熟需要选择性消除突触连接。尽管神经元内在机制在这个过程中很重要，但人们越来越认识到，神经胶质细胞也起着关键作用。如果这些细胞不能正常发挥功能，突触接触的数量、形态和功能就会发生深刻变化，导致连接异常和行为异常。除了在突触细化中的作用外，神经胶质细胞还与成年后损伤或神经系统退化时病理性突触丢失和功能障碍有关。尽管调节神经胶质细胞介导的突触消除的机制仍在被揭示，但很明显，这个复杂的过程涉及许多促进和抑制特定突触连接去除的线索。更深入地了解这些信号以及不同细胞类型的贡献，不仅将有助于深入了解这一关键的生物学事件，而且对于推进大脑发育和神经疾病的知识也很重要。
