TY - JOUR T1 - Morphological and phagocytic profile of microglia in the developing rat cerebellum JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0036-15.2015 SP - ENEURO.0036-15.2015 AU - Miguel Perez-Pouchoulen AU - Jonathan W. VanRyzin AU - Margaret M. McCarthy Y1 - 2015/08/18 UR - http://www.eneuro.org/content/early/2015/08/18/ENEURO.0036-15.2015.abstract N2 - Microglia are being increasingly recognized as playing important roles in neurodevelopment. The cerebellum matures postnatally, undergoing major growth, but the role of microglia in the developing cerebellum is not well understood. Using the laboratory rat we quantified and morphologically categorized microglia throughout the vermis and across development using a design-based unbiased stereology method. We found that microglial morphology changed from amoeboid to ramified during the first three postnatal weeks in a region specific manner. These morphological changes were accompanied by the sudden appearance of phagocytic cups during the third postnatal week from PN17 to PN19, with a >4-fold increase compared to the first week, followed by a prompt decline at the end of the third week. The microglial phagocytic cups were significantly higher in the granular layer (∼69%) than in the molecular layer (∼31%; ML) during a three-day window, and present on ∼67% of microglia with thick processes and ∼33% of microglia with thin processes. Similar proportions of phagocytic cups associated to microglia with either thick or thin processes were found in the ML. We observed cell nuclei fragmentation and cleaved caspase-3 expression within some microglial phagocytic cups, presumably from dying granule neurons. At PN17 males showed a ∼ 2-fold increase in microglia with thin processes compared to females. Our findings indicate a continuous process of microglial maturation and a non-uniform distribution of microglia in the cerebellar cortex that implicates microglia as an important cellular component of the developing cerebellum.Significance Statement: Microglia are the resident immune cells of the brain and constantly survey their local environment in order to eliminate cellular debris after injury or infection. During brain development, microglia participate in neurite growth, synaptic pruning, and apoptosis, all of which are essential processes to the establishment of neuronal circuits. The cerebellum undergoes major growth and synaptic reorganization after birth, leading to the development of cerebellar circuits which are involved in motor and cognitive functions. The role of microglia in the developing cerebellum is not well understood. This study provides important foundational profiles of microglial development in the cerebellum, a vulnerable structure to alteration during development, and contributes to the growing appreciation of the clearance activity of microglia during postnatal development. ER -