Microglial depletion disrupts normal functional development of adult-born neurons in the olfactory bulb.

Jenelle Wallace,Julia Lord,Venkatesh N Murthy,Beth Stevens,Lasse Dissing-Olesen

doi:10.7554/elife.50531

Jenelle Wallace, Julia Lord + Show 3 more

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https://doi.org/10.7554/elife.50531

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Abstract

Microglia play key roles in regulating synapse development and refinement in the developing brain, but it is unknown whether they are similarly involved during adult neurogenesis. By transiently depleting microglia from the healthy adult mouse brain, we show that microglia are necessary for the normal functional development of adult-born granule cells (abGCs) in the olfactory bulb. Microglial depletion reduces the odor responses of developing, but not preexisting GCs in vivo in both awake and anesthetized mice. Microglia preferentially target their motile processes to interact with mushroom spines on abGCs, and when microglia are absent, abGCs develop smaller spines and receive weaker excitatory synaptic inputs. These results suggest that microglia promote the development of excitatory synapses onto developing abGCs, which may impact the function of these cells in the olfactory circuit.

Highlights

Microglia are critically important for normal brain development in the embryonic and early postnatal stages (Hammond et al, 2018)
Microglia seem well-positioned to perform similar roles to facilitate the integration of adult-born neurons into circuits in the adult brain in the dentate gyrus (DG) and olfactory bulb (OB) (Ekdahl, 2012; Rodrıguez-Iglesias et al, 2019), most studies on microglial regulation of adult neurogenesis to date have focused on early stages of the process occurring in the neurogenic niches
To visualize interactions between microglia and adult-born granule cells (abGCs), we performed time-lapse in vivo two-photon imaging of the dendrites of dTomato-labeled abGCs in the external plexiform layer (EPL) of the OB over the first four weeks after injection in CX3CR1-GFP +/- mice, in which microglia are labeled with GFP (Video 1, Figure 1A)

Summary

Introduction

Microglia are critically important for normal brain development in the embryonic and early postnatal stages (Hammond et al, 2018). Microglia have been implicated in the regulation of synaptic development, including activity-dependent synaptic pruning (Stevens et al, 2007; Schafer et al, 2012; Tremblay et al, 2010; Paolicelli et al, 2011; Gunner et al, 2019) on one hand and promotion of synaptic development and maturation on the other (Hoshiko et al, 2012; Zhan et al, 2014; Miyamoto et al, 2016; Nakayama et al, 2018). Microglia seem well-positioned to perform similar roles to facilitate the integration of adult-born neurons into circuits in the adult brain in the dentate gyrus (DG) and olfactory bulb (OB) (Ekdahl, 2012; Rodrıguez-Iglesias et al, 2019), most studies on microglial regulation of adult neurogenesis to date have focused on early stages of the process occurring in the neurogenic niches. Hippocampal adult neurogenesis is impaired in models of neuroinflammation (Monje et al, 2003; Ekdahl et al, 2003) and in immune-

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