Microglia, the major immune cells of the brain, are functionally heterogeneous but in vivo functional properties of these cells are rarely studied at single-cell resolution. By using microRNA-9 regulated viral vectors for multicolor labeling and longitudinal in vivo monitoring of individual microglia, we followed their fate in the cortex of healthy adult mice and at the onset of amyloidosis in a mouse model of Alzheimer's disease. In wild-type mice, microglia were rather mobile (16% of the cells migrated at least once in 10–20 days) but had a low turnover as documented by low division and death rates.
Microglia arise from the yolk sac and enter the brain during early embryogenesis. Upon entry, microglia undergo in situ proliferation and eventually colonize the entire brain by the third postnatal week in mice. However, the intricacies of their developmental expansion remain unclear. Here, we characterize the proliferative dynamics of microglia during embryonic and postnatal development using complementary fate-mapping techniques. We demonstrate that the developmental colonization of the brain is facilitated by clonal expansion of highly proliferative microglial progenitors that occupy spatial niches throughout the brain.
Adult-born cells, arriving daily into the rodent olfactory bulb, either integrate into the neural circuitry or get eliminated. However, whether these two populations differ in their morphological or functional properties remains unclear. Using longitudinal in vivo two-photon imaging, we monitored dendritic morphogenesis, odor-evoked responsiveness, ongoing Ca2+ signaling, and survival/death of adult-born juxtaglomerular neurons (abJGNs). We found that the maturation of abJGNs is accompanied by a significant reduction in dendritic complexity, with surviving and subsequently eliminated cells showing similar degrees of dendritic remodeling.
The development and survival of adult-born neurons are believed to be driven by sensory signaling. Here, in vivo analyses of motility, morphology and Ca2+ signaling, as well as transcriptome analyses of adult-born juxtaglomerular cells with reduced endogenous excitability (via cell-specific overexpression of either Kv1.2 or Kir2.1 K+ channels), revealed a pronounced impairment of migration, morphogenesis, survival, and functional integration of these cells into the mouse olfactory bulb, accompanied by a reduction in cytosolic Ca2+ fluctuations, phosphorylation of CREB and pCREB-mediated gene expression.
Diffuse gliomas, particularly glioblastomas, are incurable brain tumours. They are characterized by networks of interconnected brain tumour cells that communicate via Ca2+ transients. However, the networks’ architecture and communication strategy and how these influence tumour biology remain unknown. Here we describe how glioblastoma cell networks include a small, plastic population of highly active glioblastoma cells that display rhythmic Ca2+ oscillations and are particularly connected to others. Their autonomous periodic Ca2+ transients preceded Ca2+ transients of other network-connected cells, activating the frequency-dependent MAPK and NF-κB pathways.
The sense of smell supports the identification and the safety of food, warns of danger/predators, and plays a key role in mating (Croy and Hummel, 2017; Kondo et al., 2020; Tzeng et al., 2021). Via connection to the limbic system, it supports behavioral adaption and emotions and can detect fear, tears, and happiness in the body odor of others (Croy and Hummel, 2017; Tzeng et al., 2021).
Trypanosoma brucei is the causative agent of human African trypanosomiasis. The parasite transmigrates from blood vessels across the choroid plexus epithelium to enter the central nervous system, a process that leads to the manifestation of second stage sleeping sickness. Using an in vitro model of the blood-cerebrospinal fluid barrier, we investigated the mechanism of the transmigration process.
The cuprizone model is a widely used model to study the pathogenesis of multiple sclerosis (MS). Due to the selective loss of mature oligodendrocytes and myelin, it is mainly being used to study demyelination and the mechanisms of remyelination, as well as the efficiency of compounds or therapeutics aiming at remyelination. Although early investigations using high dosages of cuprizone reported the occurrence of hydrocephalus, it has long been assumed that cuprizone feeding at lower dosages does not induce changes at the blood–brain barrier (BBB).
Under physiological conditions microglia, the immune sentinels of the brain, constantly monitor their microenvironment. In the case of danger, damage or cell/tissue dyshomeostasis, they react with changes in process motility, polarization, directed process movement, morphology and gene expression profile; release pro- and anti-inflammatory mediators; proliferate; and clean brain parenchyma by means of phagocytosis.
Intrinsic neuronal activity is a hallmark of the developing brain. In rodents, a handful of such activities were described in different cortical areas but the unifying macroscopic perspective is still lacking.