Microglia regulate nucleus accumbens synaptic development and circuit function underlying threat avoidance behaviors.

While CNS microglia have well-established roles in synapse pruning during neurodevelopment, only a few studies have identified roles for microglia in synapse formation. These studies focused on the cortex and primary sensory circuits during restricted developmental time periods, leaving substantial gaps in our understanding of the early developmental functions of microglia. Here we investigated how the absence of microglia impacts synaptic development in the nucleus accumbens (NAc), a region critical for emotional regulation and motivated behaviors and where dysfunction is implicated in psychiatric disorders that arise early in life.

Serotonin sensing by microglia conditions the proper development of neuronal circuits and of social and adaptive skills.

The proper maturation of emotional and sensory circuits requires fine-tuning of serotonin (5-HT) level during early postnatal development. Consistently, dysfunctions of the serotonergic system have been associated with neurodevelopmental psychiatric diseases, including autism spectrum disorders (ASD). However, the mechanisms underlying the developmental effects of 5-HT remain partially unknown, one obstacle being the action of 5-HT on different cell types.

Microglia Drive Pockets of Neuroinflammation in Middle Age.

During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to CNS insults, positioning these cells to have profound impact on the function of nearby neurons. We and others recently showed that microglial attributes differ significantly across brain regions in young adult mice. However, the degree to which microglial properties vary during aging is largely unexplored.

The serotonin 2B receptor is required in neonatal microglia to limit neuroinflammation and sickness behavior in adulthood.

Severe peripheral infections induce an adaptive sickness behavior and an innate immune reaction in various organs including the brain. On the long term, persistent alteration of microglia, the brain innate immune cells, is associated with an increased risk of psychiatric disorders. It is thus critical to identify genes and mechanisms controlling the intensity and duration of the neuroinflammation induced by peripheral immune challenges.

Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices.

Microglial cells are resident innate immune cells of the brain that constantly scan their environment with their long processes and, upon disruption of homeostasis, undergo rapid morphological changes. For example, a laser lesion induces in a few minutes an oriented growth of microglial processes, also called "directional motility", toward the site of injury. A similar effect can be obtained by delivering locally ATP or serotonin (5-hydroxytryptamine [5-HT]).