Microglia play important roles in perinatal neuro- and synapto-genesis. To test the role of microglia in these processes during adulthood, we examined the effects of microglia depletion, via treatment of mice with the CSF-1 receptor antagonist PLX5622, and abrogated neuronal-microglial communication in CX3C receptor-1 deficient (Cx3cr1−/−) mice. Microglia depletion significantly lowered spine density in young (developing) but not mature adult-born-granule-cells (abGCs) in the olfactory bulb. Two-photon time-lapse imaging indicated that microglia depletion reduced spine formation and elimination. Functionally, odor-evoked responses of mitral cells, which are normally inhibited by abGCs, were increased in microglia-depleted mice. In Cx3cr1−/− mice, abGCs exhibited reduced spine density, dynamics and size, concomitantly with reduced contacts between Cx3cr1-deficient microglia and abGCs' dendritic shafts, along with increased proportion of microglia-contacted spines. Thus, during adult neurogenesis, microglia regulate the elimination (pruning), formation, and maintenance of synapses on newborn neurons, contributing to the functional integrity of the olfactory bulb circuitry.

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Microglia play important roles in perinatal neuro-and synapto-genesis. To test the role of microglia in these processes during adulthood, we examined the effects of microglia depletion, via treatment of mice with the CSF-1 receptor antagonist PLX5622, and abrogated neuronalmicroglial communication in CX3C receptor-1 deficient (Cx3cr1 À/À ) mice. Microglia depletion significantly lowered spine density in young (developing) but not mature adult-born-granule-cells (abGCs) in the olfactory bulb. Two-photon time-lapse imaging indicated that microglia depletion reduced spine formation and elimination. Functionally, odor-evoked responses of mitral cells, which are normally inhibited by abGCs, were increased in microglia-depleted mice. In Cx3cr1 À/À mice, abGCs exhibited reduced spine density, dynamics and size, concomitantly with reduced contacts between Cx3cr1-deficient microglia and abGCs' dendritic shafts, along with increased proportion of microglia-contacted spines. Thus, during adult neurogenesis, microglia regulate the elimination (pruning), formation, and maintenance of synapses on newborn neurons, contributing to the functional integrity of the olfactory bulb circuitry.

SUMMARYThe ability to group sensory stimuli into categories is crucial for efficient interaction with a rich and ever-changing environment. In olfaction, basic features of categorical representation of odours were observed as early as in the olfactory bulb (OB). Categorical representation was described in mitral cells (MCs) as sudden transitions in responses to odours that were morphed along a continuum. However, it remains unclear to what extent such response dynamics actually reflects perceptual categories and decisions therein. Here, we tested the role of learning on category formation in the mouse OB, using in vivo two-photon calcium imaging and behaviour. We imaged MCs responses in naïve mice and in awake behaving mice as they learned two tasks with different classification logic. In one task, a 1-decision boundary task, animals learned to classify odour mixtures based on the dominant compound in the mixtures. As expected, categorical representation of close by odours, which was evident already in naïve animals, further increased following learning. In a second task, a multi-decision boundary task, animals learned to classify odours independent of their chemical similarity. Rather, odour discrimination was based on the meaning ascribed to them (either rewarding or not). Following the second task, odour representations by MCs reorganized according to the odour value in the new category. This functional reorganization was also reflected as a shift from predominantly excitatory odour responses to predominantly inhibitory odour responses. Our data shows that odour representations by MCs is flexible, shaped by task demands, and carry category-related information.

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