Endogenous activity regulates the early development of adult-born neurons in the mouse olfactory bulb

Thousands of adult-born neurons are added to the mouse olfactory bulb on a daily basis. The mechanisms underlying the migration, morphogenesis and survival of adult-born neurons are not well understood. In the present work, we studied the roles of endogenous and sensory-driven neuronal activity in the in vivo development of adult-born neurons in the mouse olfactory bulb. We utilized the overexpression of potassium channel, Kv1.2 or Kir2.1, to genetically modify the endogenous activity of adult-born neurons. By using in vivo two-photon Ca2+ imaging in awake mice, we found a ubiquitous presence of spontaneous Ca2+ transients in control and even Kv1.2- and Kir2.1-overexpressing adult-born neurons. The overexpression of Kv1.2 or Kir2.1 selectively changed the spiking behavior of frequently or even continuously active cells by decreasing their fraction as well as their area under the curve and the maximum Twitch-2B ratio. We further monitored the in vivo development of these Kv1.2- and Kir2.1-overexpressing adult-born neurons and discovered that their migration, morphogenesis, odor-evoked responsiveness, and early-phase (14-25 DPI) survival rate were remarkably impaired. Furthermore, whereas Kv1.2-overexpressing adult-born neurons showed similar survival rate as control cells during the late-phase (25-45 DPI) survival, the Kir2.1-overexpressing cells showed significantly lower survival rate. It is probably because, unlike Kv1.2 overexpression which solely altered endogenous activity, Kir2.1 overexpression impaired both endogenous and sensory-driven activity. These data suggest that the survival of adult-born neurons was predominantly regulated by endogenous activity in the early phase and by sensory-driven activity in the late phase. Furthermore, we tested the role of sensory-driven activity in the development of adult-born neurons. The odor-deprived adult-born neurons displayed normal migration and morphology, thus suggesting that sensory-driven activity did not affect the early development of adult-born neurons. Further analysis revealed that the odor-deprived adult-born neurons maintained a normal level of endogenous activity. We also explored the interplay between endogenous and sensory-driven activity. Using in vivo Ca2+ imaging of individual cells, we found that impaired endogenous activity was paralleled by suppressed sensory-driven activity. However, odor deprivation did not change the properties of spontaneous activity in adult-born neurons. This data suggest that endogenous activity is robust in immature adult-born neurons. Finally, we explored which signaling pathway is involved in the development of adult-born neurons. Our results demonstrated that pCREB expression was down-regulated in Kv1.2- and Kir2.1-overexpressing adult-born neurons. We propose that impaired endogenous neuronal activity inhibits Ca2+-pCREB signaling pathway as well as the expression of pCREB-dependent genes. In conclusion, our data demonstrate that endogenous but not sensory-driven activity plays a key role in regulating migration, morphogenesis and early-phase survival of adult-born neurons in the mouse olfactory bulb, and identify an important role of Kv1.2/Kir2.1 in the developmental processes mentioned above. Furthermore, our work also identifies CREB signaling pathway as a mediator of the early development of adult-born neurons. Moreover, sensory-driven activity predominantly regulates neuronal survival in the late phase

Ferromagnetic half levitation of LK-99-like synthetic samples

We successfully synthesized polycrystalline LK-99-like ceramic samples with a solid-state-sintering method. Powder X-ray diffraction shows that the main contents are $\mathrm{Pb_{10-x}Cu_x(PO_4)_6O}$ and $\mathrm{Cu_2S}$, consistent with recent reports [arXiv:2307.12037; arXiv:2308.01192]. In some small flaky fragments, we successfully observed ``half levitation'' atop a $\mathrm{Nd_2Fe_{14}B}$ magnet. Using magnetization measurements on such small pieces, as well as on a large piece which does not exhibit the half levitation, we show that the samples ubiquitously contain weak yet definitive soft ferromagnetic components. We argue that, together with the pronounced shape anisotropy of the small fragments, the soft ferromagnetism is sufficient to explain the observed half levitation in strong vertical magnetic fields. Our measurements do not indicate the presence of the Meissner effect, nor zero resistance, in our samples, leading us to believe that our samples do not exhibit superconductivity. The precise chemical composition and the physics behind the ferromagnetic component remain outstanding questions to be addressed in future research.Comment: 10 pages, 10 figure

The relation between college students’ neuroticism and loneliness: The chain mediating roles of self-efficacy, social avoidance and distress

BackgroundRecently, identifying the psychological mechanism of college students’ loneliness has attracted wide attention because the maladjustment caused by college students’ loneliness is increasingly common. This study explored the relationship and potential mechanism between college students’ neuroticism and loneliness in a large sample.MethodsA total of 4,600 college students completed the Big Five Personality Scale, Loneliness Scale, Self-efficacy Scale and Social Avoidance and Distress Scale.ResultsBy examining the chain mediating roles of self-efficacy, social avoidance and distress (SAD) in the relation between neuroticism and loneliness, the present study found that college students’ neuroticism was positively associated with loneliness via self-efficacy and SAD, respectively, and sequentially.ConclusionsThe results suggest a significant positive association between neuroticism and loneliness, which is influenced by the mediating effects of both self-efficacy and social avoidance and distress (SAD), as well as the chained mediating effects of self-efficacy and SAD

Long-term in vivo single-cell tracking reveals the switch of migration patterns in adult-born juxtaglomerular cells of the mouse olfactory bulb

The behavior of adult-born cells can be easily monitored in cell culture or in lower model organisms, but longitudinal observation of individual mammalian adult-born cells in their native microenvironment still proves to be a challenge. Here we have established an approach named optical cell positioning system for long-term in vivo single-cell tracking, which integrates red-green-blue cell labeling with repeated angiography. By combining this approach with in vivo two-photon imaging technique, we characterized the in vivo migration patterns of adult-born neurons in the olfactory bulb. In contrast to the traditional view of mere radial migration of adult-born cells within the bulb, we found that juxtaglomerular cells switch from radial migration to long distance lateral migration upon arrival in their destination layer. This unique long-distance lateral migration has characteristic temporal (stop-and-go) and spatial (migratory, unidirectional or multidirectional) patterns, with a clear cell age-dependent decrease in the migration speed. The active migration of adult-born cells coincides with the time period of initial fate determination and is likely to impact on the integration sites of adult-born cells, their odor responsiveness, as well as their survival rate

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