Cell death is prevalent throughout life; however, the coordinated interactions and roles of phagocytes during corpse removal in the live brain are poorly understood. We developed photochemical and viral methodologies to induce death in single cells and combined this with intravital optical imaging. This approach allowed us to track multicellular phagocytic interactions with precise spatiotemporal resolution. Astrocytes and microglia engaged with dying neurons in an orchestrated and synchronized fashion. Each glial cell played specialized roles: Astrocyte processes rapidly polarized and engulfed numerous small dendritic apoptotic bodies, while microglia migrated and engulfed the soma and apical dendrites. The relative involvement and phagocytic specialization of each glial cell was plastic and controlled by the receptor tyrosine kinase Mertk. In aging, there was a marked delay in apoptotic cell removal. Thus, a precisely orchestrated response and cross-talk between glial cells during corpse removal may be critical for maintaining brain homeostasis.

细胞死亡在人的一生中普遍存在；然而，人们对活体大脑中尸体清除过程中吞噬细胞的协调相互作用和作用知之甚少。我们开发了光化学和病毒方法来诱导单细胞死亡，并将其与活体光学成像相结合。这种方法使我们能够以精确的时空分辨率追踪多细胞吞噬相互作用。星形胶质细胞和小胶质细胞以精心策划和同步的方式与垂死的神经元相互作用。每个神经胶质细胞都发挥着专门的作用：星形胶质细胞迅速极化并吞噬大量小的树突凋亡体，而小胶质细胞则迁移并吞噬胞体和顶端树突。每个神经胶质细胞的相对参与和吞噬特化是可塑的，并由受体酪氨酸激酶Mertk控制。在衰老过程中，凋亡细胞的清除明显延迟。因此，在尸体清除过程中，神经胶质细胞之间精确协调的反应和串扰可能对于维持大脑稳态至关重要。