RESUMEN
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RESUMEN
Microglia are the brain's resident innate immune cells and also have a role in synaptic plasticity. Microglial processes continuously survey the brain parenchyma, interact with synaptic elements and maintain tissue homeostasis. However, the mechanisms that control surveillance and its role in synaptic plasticity are poorly understood. Microglial dynamics in vivo have been primarily studied in anesthetized animals. Here we report that microglial surveillance and injury response are reduced in awake mice as compared to anesthetized mice, suggesting that arousal state modulates microglial function. Pharmacologic stimulation of ß2-adrenergic receptors recapitulated these observations and disrupted experience-dependent plasticity, and these effects required the presence of ß2-adrenergic receptors in microglia. These results indicate that microglial roles in surveillance and synaptic plasticity in the mouse brain are modulated by noradrenergic tone fluctuations between arousal states and emphasize the need to understand the effect of disruptions of adrenergic signaling in neurodevelopment and neuropathology.
Asunto(s)
Microglía/fisiología , Plasticidad Neuronal/fisiología , Norepinefrina/fisiología , Corteza Visual/fisiología , Animales , Bencilaminas/farmacología , Receptor 1 de Quimiocinas CX3C/genética , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Ritmo Circadiano/fisiología , Clenbuterol/farmacología , Dexmedetomidina/farmacología , Predominio Ocular , Femenino , Fentanilo/farmacología , Locus Coeruleus/efectos de los fármacos , Masculino , Ratones , Ratones Transgénicos , Microglía/citología , Microglía/efectos de los fármacos , Nadolol/farmacología , Plasticidad Neuronal/efectos de los fármacos , Neuronas/metabolismo , Neuronas/fisiología , Norepinefrina/metabolismo , Propanolaminas/farmacología , Restricción Física/fisiología , Terbutalina/farmacología , Vigilia , Heridas y Lesiones/fisiopatologíaRESUMEN
Microglia are the innate immune cells of the central nervous system and are also important participants in normal development and synaptic plasticity. Here, we demonstrate that the microglia of the mouse cerebellum represent a unique population compared to cortical microglia. Microglia are more sparsely distributed within the cerebellum and have a markedly less ramified morphology compared to their cortical counterparts. Using time-lapse in vivo imaging, we found that these differences in distribution and morphology ultimately lead to decreased parenchymal surveillance by cerebellar microglia. We also observed a novel form of somal motility in cerebellar microglia in vivo, which has not been described in cortical populations. We captured microglial interactions with Purkinje neurons in vivo. Cerebellar microglia interact dynamically with both the dendritic arbors and somas of Purkinje neurons. These findings suggest that cerebellar microglia are physiologically distinct from cortical populations and that these differences may ultimately alter how they could contribute to plasticity and disease processes in the cerebellum. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 627-644, 2018.