Trends in Neurosciences
ReviewLittle cells of the little brain: microglia in cerebellar development and function
Section snippets
Cerebellar microglia in the light of microglial heterogeneity
Microglia, the innate immune cells of the CNS, directly shape and influence neural development and function. Classically studied for their roles in pathology, it is becoming increasingly clear that even under homeostatic conditions, microglia are not quiescent sentinels but actively survey and patrol the CNS and are able to respond rapidly to chemotactic cues [1,2]. As they do so, they make frequent transient contacts with neural elements [3], eliminate synapses [4,5], and influence the
Cerebellar microglia show unique functional dynamics
As mentioned, microglial dynamics have thus far been studied largely in the context of cortical microglia. Cortical microglia are highly ramified and regularly tile the neocortex, maintaining nonoverlapping territories. In vivo and brain slice time-lapse imaging experiments have shown that the cell bodies of these microglia are fairly stationary, while a very motile process arbor samples the defined territory of each cell. These microglia also rapidly respond to injury. For instance, following
Microglia are essential to cerebellar development
Microglia are integral to the developing nervous system and have been shown to influence synaptic remodeling in diverse regions such as the developing lateral geniculate nucleus (LGN) [4,5], primary visual [3,7,29] and somatosensory [6,70] cortices, and the hippocampus [14,15,71]. In these areas, microglia interact with synapses to restructure synaptic inputs, often in an activity-/experience-dependent manner that has been linked to their ability to phagocytose or trogocytose synaptic material [
Concluding remarks and future directions
Mounting evidence suggests that cerebellar microglia are distinct from other microglial cell populations, as demonstrated by their differential morphology, distribution, and dynamics [29]. These characteristics arise from altered transcriptomics, epigenetics, and signaling pathways within cerebellar microglia and cerebellum-specific environmental cues [11,19,20,66]. Many of these differences may have their origins in cerebellar development, where microglia clear entire apoptotic neuronal cell
Acknowledgments
This work was supported by National Institutes of Health (NIH) grants R01 NS114480, AA02711 (A.K.M.), and F31NS120609 (M.B.S.), as well as by grants from the Schmitt Program in Integrative Neuroscience and Harry T. Mangurian Jr. Foundation.
Declaration of interests
The authors declare no competing interests in relation to this work.
Glossary
- Climbing fiber (CF)
- a projection fiber from the inferior olivary nucleus to cerebellar Purkinje cells, thought to encode sensory information. Each Purkinje cell is innervated by a single climbing fiber, although this single fiber makes thousands of synapses onto the Purkinje cell dendritic arbor. The CF is one of the two excitatory inputs to Purkinje cells.
- Disease-associated microglia (DAM)
- a transcriptomic signature defined as suites of differentially expressed genes in microglia during disease
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