Endogenous but not sensory-driven activity controls migration, morphogenesis and survival of adult-born juxtaglomerular neurons in the mouse olfactory bulb.

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. Moreover, K+ channel overexpression strongly downregulated genes involved in neuronal migration, differentiation, and morphogenesis and upregulated apoptosis-related genes, thus locking adult-born cells in an immature and vulnerable state. Surprisingly, cells deprived of sensory-driven activity developed normally. Together, the data reveal signaling pathways connecting the endogenous intermittent neuronal activity/Ca2+ fluctuations as well as enhanced Kv1.2/Kir2.1 K+ channel function to migration, maturation, and survival of adult-born neurons

Endogenous but Not Sensory-Driven Activity Controls Migration, Morphogenesis and Survival of Adult-Born Juxtaglomerular Neurons in the Mouse Olfactory Bulb

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. Moreover, K+ channel overexpression strongly downregulated genes involved in neuronal migration, differentiation, and morphogenesis and upregulated apoptosis-related genes, thus locking adult-born cells in an immature and vulnerable state. Surprisingly, cells deprived of sensory-driven activity developed normally. Together, the data reveal signaling pathways connecting the endogenous intermittent neuronal activity/Ca2+ fluctuations as well as enhanced Kv1.2/Kir2.1 K+ channel function to migration, maturation, and survival of adult-born neurons

Stable behavioral state-specific mesoscale activity patterns in the developing cortex of neonates

Endogenous 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. Here we combined large-scale in vivo Ca2+ imaging of the dorsal cortex in naturally behaving neonatal mice with advanced mathematical analyses to reveal unique behavioral state-specific maps of endogenous activity. These maps were remarkably stable over time within and across experiments, and used patches of correlated activity with little hemispheric symmetry as well as stationary and propagating waves as building blocks. Importantly, the maps recorded during motion and rest were almost inverse, with sensory-motor areas active during motion and posterior-lateral areas active at rest. The retrosplenial cortex engaged in both resting- and motion-related activities, building functional long-range connections with respective cortical areas. Together, these data provide so far the most complete view on the endogenous network activity pacing development of cortex-wide functional networks in neonates

In vivo mechanisms of cortical network dysfunction induced by systemic inflammation

peer reviewedPeripheral inflammation is known to impact brain function, resulting in lethargy, loss of appetite and impaired cognitive abilities. However, the channels for information transfer from the periphery to the brain, the corresponding signaling molecules and the inflammation-induced interaction between microglia and neurons remain obscure. Here, we used longitudinal in vivo two-photon Ca2+ imaging to monitor neuronal activity in the mouse cortex throughout the early (initiation) and late (resolution) phases of peripheral inflammation. Single peripheral lipopolysaccharide injection induced a substantial but transient increase in ongoing neuronal activity, restricted to the initiation phase, whereas the impairment of visual processing was selectively observed during the resolution phase of systemic inflammation. In the frontal/motor cortex, the initiation phase-specific cortical hyperactivity was seen in the deep (layer 5) and superficial (layer 2/3) pyramidal neurons but not in the axons coming from the somatosensory cortex, and was accompanied by reduced activity of layer 2/3 cortical interneurons. Moreover, the hyperactivity was preserved after depletion of microglia and in NLRP3-/- mice but absent in TNF-α-/- mice. Together, these data identify microglia-independent and TNF-α-mediated reduction of cortical inhibition as a likely cause of the initiation phase-specific cortical hyperactivity and reveal the resolution phase-specific impairment of sensory processing, presumably caused by activated microglia