Microglia are the primary immune cells of the brain and function in multiple ways to facilitate proper brain development. However, our current understanding of how these cells influence the later expression of normal behaviors is lacking. Using the laboratory rat, we administered liposomal clodronate centrally to selectively deplete microglia in the developing postnatal brain. We then assessed a range of developmental, juvenile, and adult behaviors. Liposomal clodronate treatment on postnatal days 0, 2, and 4 depleted microglia with recovery by about 10 days of age and induced a hyper-locomotive phenotype, observable in the second postnatal week. Temporary microglia depletion also increased juvenile locomotion in the open field test, and decreased anxiety-like behaviors in the open field and elevated plus maze. These same rats displayed reductions in predator-odor induced avoidance behavior, but increased their risk assessment behaviors compared to vehicle-treated controls. In adulthood, postnatal microglia depletion resulted in significant deficits in male-specific sex behaviors. Using factor analysis, we identified two underlying traits- behavioral disinhibition and locomotion- as being significantly altered by postnatal microglia depletion. These findings further implicate microglia as being critically important to the development juvenile and adult behavior.
Significance Statement: Microglia are critical regulators of postnatal brain development, a time important for the organization of neural architecture and the refinement of synaptic patterning. These immune cells engage in a range of functions from promoting cell genesis and controlling cell number, to facilitating the establishment and maturation of synaptic connections. Despite the current understanding of actions of microglia in the postnatal period, very little is known about how microglia influences on these early developmental processes affect the expression of behavior later in life. Our findings highlight the importance of microglia during this critical developmental window, and suggest the necessity of these cells for the normal expression of juvenile and adult behavior.
1 The authors declare no conflicts of interest.
3 This work was funded by NIH Grants R01-MH52716 and R01-DA039062 to M.M.M.