Highlights d In NREMS, thalamic noradrenaline (NA) levels are higher than in quiet wakefulness d Thalamic NA fluctuates over 50 s and is anticorrelated to sleep spindles d NA released from LC depolarizes thalamic neurons through a1and b-adrenoceptors d Infraslow LC activity coordinates heart-rate variations with spindles

No abstract

Dendritic cells play a key role in immune responses. There is growing evidence that reactive oxygen species participate in signaling pathways involving nuclear factor (NF)-kappaB, leading to expression of important immune system genes. We found that, unlike H2O2, reactive oxygen species generated by the reaction of oxidase on xanthine induced early phenotypic maturation of dendritic cells by upregulating specific markers CD80, CD83, and CD86 and downregulating mannose receptor-mediated endocytosis. Maturation induced by xanthine oxidase was prevented by allopurinol, an inhibitor of xanthine oxidase activity, and by N-acetylcysteine. The proteasome inhibitor MG-132, which blocks NF-kappaB activation, also inhibited CD86 upregulation, but not endocytosis downregulation by reactive oxygen species. Finally, xanthine-xanthine oxidase enhanced or blocked antigen presentation by dendritic cells depending on whether they had been prepulsed or not with the antigen. Taken together, these results demonstrate that oxidative stress induces phenotypic and functional maturation of dendritic cells, partly through an NF-kappaB-dependent mechanism.

The corpus callosum (CC) plays a crucial role in interhemispheric communication. It has been shown that CC formation relies on the guidepost cells located in the midline region that include glutamatergic and GABAergic neurons as well as glial cells. However, the origin of these guidepost GABAergic neurons and their precise function in callosal axon pathfinding remain to be investigated. Here, we show that two distinct GABAergic neuronal subpopulations converge toward the midline prior to the arrival of callosal axons. Using in vivo and ex vivo fate mapping we show that CC GABAergic neurons originate in the caudal and medial ganglionic eminences (CGE and MGE) but not in the lateral ganglionic eminence (LGE). Time lapse imaging on organotypic slices and in vivo analyses further revealed that CC GABAergic neurons contribute to the normal navigation of callosal axons. The use of Nkx2.1 knockout (KO) mice confirmed a role of these neurons in the maintenance of proper behavior of callosal axons while growing through the CC. Indeed, using in vitro transplantation assays, we demonstrated that both MGE- and CGE-derived GABAergic neurons exert an attractive activity on callosal axons. Furthermore, by combining a sensitive RT-PCR technique with in situ hybridization, we demonstrate that CC neurons express multiple short and long range guidance cues. This study strongly suggests that MGE- and CGE-derived interneurons may guide CC axons by multiple guidance mechanisms and signaling pathways.

The noradrenergic locus coeruleus (LC) supports vital brain functions during wakefulness. In contrast, the LC has been associated with sleep-promotion and -disruption, leaving its functions for sleep uncertain. Here, we show that the LC is essential for the progression of natural, undisturbed sleep because it creates a non-reducible timeframe for the non-rapid-eye-movement (NREM) sleep-REM sleep cycle. Fiber-photometric jGCaMP8s-based LC activity measures, closed-loop optogenetics and mouse sleep-wake monitoring revealed that LC showed ~50-s-activity fluctuations, during which high activity levels promoted a NREMS with high arousability, while low levels a NREMS with the opportunity for transitions to REMS. The NREMS-REMS cycle was shortened by LC inhibition due to precocious REMS onset. Supporting LC's pivotal role as a gatekeeper of the NREMS-REMS cycle, REMS entries occurred on intervals no shorter than ~50 s during REMS-restriction. A stimulus-enriched wake experience strengthened LC fluctuations, which contributed to subsequent NREMS fragmentation and delayed REMS. The LC fluctuations are hence indispensable for the NREMS-REMS cycle but they can become sleep-disruptive as a result of prior wake experience.