Newborn microglia rapidly replenish the whole brain after selective elimination of most microglia (>99%) in adult mice. Previous studies reported that repopulated microglia were largely derived from microglial progenitor cells expressing nestin in the brain. However, the origin of these repopulated microglia has been hotly debated. In this study, we investigated the origin of repopulated microglia by a series of fate-mapping approaches. We first excluded the blood origin of repopulated microglia via parabiosis. With different transgenic mouse lines, we then demonstrated that all repopulated microglia were derived from the proliferation of the few surviving microglia (<1%). Despite a transient pattern of nestin expression in newly forming microglia, none of repopulated microglia were derived from nestin-positive non-microglial cells. In summary, we conclude that repopulated microglia are solely derived from residual microglia rather than de novo progenitors, suggesting the absence of microglial progenitor cells in the adult brain.
The sense of smell allows chemicals to be perceived as diverse scents. We used single neuron RNA-Sequencing (RNA-Seq) to explore developmental mechanisms that shape this ability as nasal olfactory neurons mature in mice. Most mature neurons expressed only one of the roughly 1000 odorant receptor genes (Olfrs) available, and that at high levels. However, many immature neurons expressed low levels of multiple Olfrs. Coexpressed Olfrs localized to overlapping zones of the nasal epithelium, suggesting regional biases, but not to single genomic loci. A single immature neuron could express Olfrs from up to seven different chromosomes. The mature state in which expression of Olfr genes is restricted to one per neuron emerges over a developmental progression that appears independent of neuronal activity requiring sensory transduction molecules.
Instinctive reactions to danger are critical to the perpetuation of
species and are observed throughout the animal kingdom. The scent of predators
induces an instinctive fear response in mice that includes behavioral changes as
well as a surge in blood stress hormones that mobilizes multiple body systems to
escape impending danger1,2. How the olfactory system routes
predator signals detected in the nose to achieve these effects is unknown. Here
we identify a specific area of the olfactory cortex that induces stress hormone
responses to volatile predator odors. Using monosynaptic and polysynaptic viral
tracers, we found that multiple olfactory cortical areas transmit signals to
hypothalamic CRH (corticotropin releasing hormone) neurons, which control stress
hormone levels. However, only one minor cortical area, the amygdalo-piriform
transition area (AmPir), contained neurons upstream of CRH neurons that were
activated by volatile predator odors. Chemogenetic stimulation of AmPir
activated CRH neurons and induced an increase in blood stress hormone, mimicking
an instinctive fear response. Moreover, chemogenetic silencing of AmPir markedly
reduced the stress hormone response to predator odors without affecting a fear
behavior. These findings suggest that AmPir, a small area comprising
<5% of the olfactory cortex, plays a key role in the hormonal
component of the instinctive fear response to volatile predator scents.
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