title: Serotonin Modulates Developmental Microglia via 5-HT2B Receptors: Potential Implication during Synaptic Refinement of Retinogeniculate Projections.
abstract: Maturation of functional neuronal circuits during central nervous system development relies on sophisticated mechanisms. First, axonal and dendritic growth should reach appropriate targets for correct synapse elaboration. Second, pruning and neuronal death are required to eliminate redundant or inappropriate neuronal connections. Serotonin, in addition to its role as a neurotransmitter, actively participates in postnatal establishment and refinement of brain wiring in mammals. Brain resident macrophages, that is, microglia, also play an important role in developmentally regulated neuronal death as well as in synaptic maturation and elimination. Here, we tested the hypothesis of cross-regulation between microglia and serotonin during postnatal brain development in a mouse model of synaptic refinement. We found expression of the serotonin 5-HT2B receptor on postnatal microglia, suggesting that serotonin could participate in temporal and spatial synchronization of microglial functions. Using two-photon microscopy, acute brain slices, and local delivery of serotonin, we observed that microglial processes moved rapidly toward the source of serotonin in Htr2B(+/+) mice, but not in Htr2B(-/-) mice lacking the 5-HT2B receptor. We then investigated whether some developmental steps known to be controlled by serotonin could potentially result from microglia sensitivity to serotonin. Using an in vivo model of synaptic refinement during early brain development, we investigated the maturation of the retinal projections to the thalamus and observed that Htr2B(-/-) mice present anatomical alterations of the ipsilateral projecting area of retinal axons into the thalamus. In addition, activation markers were upregulated in microglia from Htr2B(-/-) compared to control neonates, in the absence of apparent morphological modifications. These results support the hypothesis that serotonin interacts with microglial cells and these interactions participate in brain maturation.
authors: †INSERM UMR-S 839, F75005, Paris, France.|‡Sorbonne Universités, UPMC Univ Paris 06, F75005, Paris, France.|§Institut du Fer à Moulin, 17 rue du Fer à Moulin, F75005, Paris, France.
authors: Marta
authors: M
authors: Kolodziejczak
authors: †INSERM UMR-S 839, F75005, Paris, France.|‡Sorbonne Universités, UPMC Univ Paris 06, F75005, Paris, France.|§Institut du Fer à Moulin, 17 rue du Fer à Moulin, F75005, Paris, France.
authors: Catherine
authors: C
authors: Béchade
authors: †INSERM UMR-S 839, F75005, Paris, France.|‡Sorbonne Universités, UPMC Univ Paris 06, F75005, Paris, France.|§Institut du Fer à Moulin, 17 rue du Fer à Moulin, F75005, Paris, France.
authors: Nicolas
authors: N
authors: Gervasi
authors: †INSERM UMR-S 839, F75005, Paris, France.|‡Sorbonne Universités, UPMC Univ Paris 06, F75005, Paris, France.|§Institut du Fer à Moulin, 17 rue du Fer à Moulin, F75005, Paris, France.
authors: Theano
authors: T
authors: Irinopoulou
authors: †INSERM UMR-S 839, F75005, Paris, France.|‡Sorbonne Universités, UPMC Univ Paris 06, F75005, Paris, France.|§Institut du Fer à Moulin, 17 rue du Fer à Moulin, F75005, Paris, France.
authors: Sophie M
authors: SM
authors: Banas
authors: ⊥Cytometry Facility, INSERM US24, F75005, Paris, France.|∥CNRS UMS 3633, Paris Descartes University, F75005, Paris, France.
authors: Corinne
authors: C
authors: Cordier
authors: †INSERM UMR-S 839, F75005, Paris, France.|‡Sorbonne Universités, UPMC Univ Paris 06, F75005, Paris, France.|§Institut du Fer à Moulin, 17 rue du Fer à Moulin, F75005, Paris, France.
authors: Alexandra
authors: A
authors: Rebsam
authors: †INSERM UMR-S 839, F75005, Paris, France.|‡Sorbonne Universités, UPMC Univ Paris 06, F75005, Paris, France.|§Institut du Fer à Moulin, 17 rue du Fer à Moulin, F75005, Paris, France.
authors: Anne
authors: A
authors: Roumier
authors: †INSERM UMR-S 839, F75005, Paris, France.|‡Sorbonne Universités, UPMC Univ Paris 06, F75005, Paris, France.|§Institut du Fer à Moulin, 17 rue du Fer à Moulin, F75005, Paris, France.
authors: Luc
authors: L
authors: Maroteaux
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000254:growth & development / Q000502:physiology; D005829:Geniculate Bodies / Q000254:growth & development* / Q000502:physiology; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000254:growth & development* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D046509:Tissue Culture Techniques; D014795:Visual Pathways / Q000254:growth & development / Q000502:physiology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D044402:Receptor, Serotonin, 5-HT2A; D019707:Receptors, Chemokine; D012701:Serotonin
keywords: mice; microglia; postnatal development; retinal projections; serotonin receptors; thalamus