Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone

The adrenal hormone corticosterone transcriptionally regulates responsive genes in the rodent hippocampus through nuclear mineralocorticoid and glucocorticoid receptors. Via this genomic pathway the hormone alters properties of hippocampal cells slowly and for a prolonged period. Here we report that corticosterone also rapidly and reversibly changes hippocampal signaling. Stress levels of the hormone enhance the frequency of miniature excitatory postsynaptic potentials in CA1 pyramidal neurons and reduce paired-pulse facilitation, pointing to a hormone-dependent enhancement of glutamate-release probability. The rapid effect by corticosterone is accomplished through a nongenomic pathway involving membrane-located receptors. Unexpectedly, the rapid effect critically depends on the classical mineralocorticoid receptor, as evidenced by the effectiveness of agonists, antagonists, and brain-specific inactivation of the mineralocorticoid but not the glucocorticoid receptor gene. Rapid actions by corticosterone would allow the brain to change its function within minutes after stress-induced elevations of corticosteroid levels, in addition to responding later through gene-mediated signaling pathways

Diffusion on networked systems is a question of time or structure

Network science investigates the architecture of complex systems to understand their functional and dynamical properties. Structural patterns such as communities shape diffusive processes on networks. However, these results hold under the strong assumption that networks are static entities where temporal aspects can be neglected. Here we propose a generalized formalism for linear dynamics on complex networks, able to incorporate statistical properties of the timings at which events occur. We show that the diffusion dynamics is affected by the network community structure and by the temporal properties of waiting times between events. We identify the main mechanism—network structure, burstiness or fat tails of waiting times—determining the relaxation times of stochastic processes on temporal networks, in the absence of temporal–structure correlations. We identify situations when fine-scale structure can be discarded from the description of the dynamics or, conversely, when a fully detailed model is required due to temporal heterogeneities

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for $r > 0.003$ at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of $r < 0.001$ at $95\%$ CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447

Daytime sleep and performance following a zolpidem and melatonin cocktail

Pharmacologic enhancement of daytime sleep may help sustain optimal cognitive performance. At effective doses, zolpidem induces sleep but also impairs performance. Combining melatonin with low-dose zolpidem may promote daytime sleep without exacerbating performance impairments seen with high-dose zolpidem alone. Following an 8-hour undisturbed nighttime sleep period, 80 subjects (50 men, 30 women) were administered oral zolpidem 0, 5, 10, or 20 mg at 10:00 am (n = 20 per group) and then oral melatonin 0 or 5 mg at 10:30 am (thus, n = 10 per drug combination) in a double-blind randomized fashion. Subjects napped from 10:00 am to 11:30 am, at which time they were awakened and cognitive tests administered (Restricted Reminding, Paired-Associates, and Psychomotor Vigilance). A second nap ensued from 12:45 pm to 4:00 pm, followed immediately by further testing. Melatonin 5 mg plus zolpidem 0 mg enhanced daytime sleep (P .05). Zolpidem 20 mg plus melatonin 0 mg also enhanced daytime sleep (albeit nonsignificantly), but memory and vigilance were impaired (P < .05). Melatonin's sleep-promoting effects were not evident until the second nap. No advantages to administering melatonin plus zolpidem "cocktails" were evident. Unlike zolpidem, melatonin 5 mg alone improved daytime sleep without impairing memory and vigilance. Functional coupling of sleep-inducing and memory-impairing effects may be specific to benzodiazepine-receptor agonists such as zolpidem, suggesting potential advantages to using melatonin in the operational environment. That melatonin's sleep-promoting effects were delayed for several hours presents a practical consideration that may limit melatonin's usefulness when daytime sleep periods cannot be reliably anticipated or planned in advance

Représentation et pouvoir

Parmi les questions auxquelles l’histoire de la Révolution française n’a pas donné de réponses définitives, la définition « du » politique demeure toujours irrésolue. Cette indécision est d’autant plus grande que l’historiographie actuelle ne s’intéresse plus seulement aux « grands » hommes mais qu’elle prend en compte les multiples interventions dans le « domaine politique ». Entrent en ligne de compte toutes les actions symboliques et culturelles qui donnent du sens à la période. Au premier plan des interrogations se trouvent alors les représentations que les hommes et les femmes de la fin du xviiie et du début du xixe siècles ont mobilisées pour peser sur le destin collectif. L’objet du livre est l’étude de la confrontation de ces représentations mentales, linguistiques, iconographiques et rituelles et du pouvoir, exercé, contesté, imaginé pour bâtir « le » politique. L’ouvrage rassemble les communications présentées lors d’un colloque international tenu à Paris en juin 2004, réunissant des spécialistes français, américains et allemands. Tout l’éventail des médias, des pratiques et des espaces de « la politique symbolique » a été parcouru par les auteurs : de la peinture aux symboles abstraits et aux arts graphiques, des discours et des pamphlets politiques aux chansons révolutionnaires, du théâtre et des fêtes aux banquets et aux cérémonies funéraires. Entre 1789-1830 la lutte est permanente autour de telles représentations. Les acteurs politiques rivalisent entre eux pour accaparer le pouvoir d’interprétation officiel et imposer leur propre vision de « l’unique » représentation de la société. Or aucune interprétation officielle ne survit pendant longtemps. Le présent volume participe au débat sur le caractère intrinsèque de la société contemporaine, condamnée à gérer la tension inévitable entre sa volonté d’unité et les conflits qui la menacent. Comme pour d’autres domaines, la Révolution française est bien ce « laboratoire » contenant en germe les éléments déterminants des conflits à venir