Spatial memory engram in the mouse retrosplenial cortex

Memory relies on lasting adaptations of neuronal properties elicited by stimulus-driven plastic changes [1]. The strengthening (and weakening) of synapses results in the establishment of functional ensembles. It is presumed that such ensembles (or engrams) are activated during memory acquisition and re-activated upon memory retrieval. The retrosplenial cortex (RSC) has emerged as a key brain area supporting memory [2], including episodic and topographical memory in humans [3, 4, 5], as well as spatial memory in rodents [6, 7]. Dysgranular RSC is densely connected with dorsal stream visual areas [8] and contains place-like and head-direction cells, making it a prime candidate for integrating navigational information [9]. While previous reports [6, 10] describe the recruitment of RSC ensembles during navigational tasks, such ensembles have never been tracked long enough to provide evidence of stable engrams and have not been related to the retention of long-term memory. Here, we used in vivo 2-photon imaging to analyze patterns of activity of over 6,000 neurons within dysgranular RSC. Eight mice were trained on a spatial memory task. Learning was accompanied by the gradual emergence of a context-specific pattern of neuronal activity over a 3-week period, which was re-instated upon retrieval more than 3 weeks later. The stability of this memory engram was predictive of the degree of forgetting; more stable engrams were associated with better performance. This provides direct evidence for the interdependence of spatial memory consolidation and RSC engram formation. Our results demonstrate the participation of RSC in spatial memory storage at the level of neuronal ensembles

Maternal selenium intake and selenium status during pregnancy in relation to preeclampsia and pregnancy-induced hypertension in a large Norwegian Pregnancy Cohort Study

Background: Pregnancy-induced hypertensive disorders (PIHD), including preeclampsia, cause maternal and perinatal morbidity and mortality worldwide. Several studies have linked selenium supplementation and selenium status to the risk of preeclampsia, but there are no published prospective population-based studies examining associations between dietary selenium intake and preeclampsia. Aim: To examine associations between selenium intake from diet and supplements and selenium blood status and PIHD incidence, with sub-analyses for pregnancy-induced hypertension (PIH) and preeclampsia, in a large pregnancy cohort. Method: The study is based on 69,972 singleton pregnancies from the Norwegian Mother, Father and Child Cohort Study. Maternal dietary selenium intake was assessed with a validated, semi-quantitative food frequency questionnaire at about gestational week 22. Maternal selenium concentrations were measured in whole blood collected around gestational week 18 in a subset of 2572 women. Preeclampsia and PIH diagnosges were obtained from the Medical Birth Registry of Norway. Results: Participants had a median dietary selenium intake of 53 μg/day (IQR 44–62). Dietary selenium intake was not significantly associated with PIHD (adjusted (a) OR 1.03, 95% CI 0.98, 1.08 per SD of selenium intake), preeclampsia or PIH. Threshold analyses for deciles of dietary selenium intake did not show any significant associations. Neither inorganic (aOR 1.01, 95% CI 0.98, 1.05) or organic selenium supplement intake (aOR 0.98, 95% CI 0.95, 1.02) or selenium blood status was significantly associated with PIHD (aOR 1.03, 95% CI 0.86, 1.22) or PIHD subgroups. Conclusion: No significant associations were found between reported selenium intake from diet, or dietary supplements or whole-blood selenium status and PIHD in general or preeclampsia specifically. Hence, the results of this large population-based study, with selenium intake close to the recommended daily intake, do not support previous findings indicating a possible protective effect of selenium supplementation or selenium status with regard to preeclampsia incidence

Maternal probiotic milk intake during pregnancy and breastfeeding complications in the Norwegian Mother and Child Cohort Study

Purpose: During the time of breastfeeding, a third of all women contract (or: fall ill in) mastitis—the leading cause of precocious weaning. Recent studies indicate that probiotics intake may prevent mastitis by altering the breast’s bacterial flora. The aim of this study was to examine whether probiotic milk intake during pregnancy is associated with less breastfeeding complications and longer breastfeeding duration. Methods: This study included 57,134 women, with live singleton term births, participating in the Norwegian Mother and Child Cohort Study. Probiotic milk intake during the first half of pregnancy was self-reported in a validated food frequency questionnaire at gestational week 22. At 6 month postpartum, women reported complications, including mastitis, and duration and exclusivity of breastfeeding. The association between probiotic milk intake and breastfeeding complications and duration was studied by adjusted logistic regression models. Results: Probiotic milk intake was associated with increased risk for mastitis [adjusted odds ratio (aOR) 1.09, 95% confidence interval (CI) 1.02–1.16] and for any breastfeeding problems during the first month (aOR 1.19, 95% CI 1.10–1.21). However, cessation of predominant (aOR 0.95, 95% CI 0.91–0.96) or any (aOR 0.79, 95%\ua0CI 0.75–0.84) breastfeeding earlier than at 4 months was less frequent in probiotic milk consumers than in non-consumers. Conclusions: Even though probiotic milk intake during the first half of pregnancy was statistically associated with increased risk for breastfeeding complications, including mastitis, the association is probably not causal. Probiotics intake was namely associated with longer breastfeeding duration and there was indication of socioeconomic confounding. Further studies, i.e., large randomized-controlled trials, are needed to understand the association between probiotic intake and breastfeeding complications

Inter-areal coordination of columnar architectures during visual cortical development

The occurrence of a critical period of plasticity in the visual cortex has long been established, yet its function in normal development is not fully understood. Here we show that as the late phase of the critical period unfolds, different areas of cat visual cortex develop in a coordinated manner. Orientation columns in areas V1 and V2 become matched in size in regions that are mutually connected. The same age trend is found for such regions in the left and right brain hemisphere. Our results indicate that a function of critical period plasticity is to progressively coordinate the functional architectures of different cortical areas - even across hemispheres.Comment: 30 pages, 1 table, 6 figure

Maternal dietary selenium intake during pregnancy and neonatal outcomes in the norwegian mother, father, and child cohort study

Properly working antioxidant defence systems are important for fetal development. One of the nutrients with antioxidant activity is selenium. Increased maternal selenium intake has been associated with reduced risk for being small for gestational age and preterm delivery. Based on the Norwegian Mother, Father, and Child Cohort Study and the Medical Birth Registry of Norway, we in-vestigated the association of maternal selenium intake from food and dietary supplements during the first half of pregnancy (n = 71,728 women) and selenium status in mid-pregnancy (n = 2628 women) with neonatal health, measured as two composite variables (neonatal morbidity/mortality and neonatal intervention). Low maternal dietary selenium intake (<30 \ub5g/day) was associated with increased risk for neonatal morbidity/mortality (adjusted odds ratio (adjOR) 1.36, 95% confidence interval (95% CI) 1.08–1.69) and neonatal intervention (adjOR 1.16, 95% CI 1.01–1.34). Using continuous variables, there were no associations between maternal selenium intake (from diet or supplements) or whole-blood selenium concentration and neonatal outcome in the adjusted models. Our findings suggest that sufficient maternal dietary selenium intake is associated with neonatal outcome. Adher-ing to the dietary recommendations may help ensure an adequate supply of selenium for a healthy pregnancy and optimal fetal development

Stable encoding of visual cues in the mouse retrosplenial cortex

The rodent retrosplenial cortex (RSC) functions as an integrative hub for sensory and motor signals, serving roles in both navigation and memory. While RSC is reciprocally connected with the sensory cortex, the form in which sensory information is represented in the RSC and how it interacts with motor feedback is unclear and likely to be critical to computations involved in navigation such as path integration. Here, we used 2-photon cellular imaging of neural activity of putative excitatory (CaMKII expressing) and inhibitory (parvalbumin expressing) neurons to measure visual and locomotion evoked activity in RSC and compare it to primary visual cortex (V1). We observed stimulus position and orientation tuning, and a retinotopic organization. Locomotion modulation of activity of single neurons, both in darkness and light, was more pronounced in RSC than V1, and while locomotion modulation was strongest in RSC parvalbumin-positive neurons, visual-locomotion integration was found to be more supralinear in CaMKII neurons. Longitudinal measurements showed that response properties were stably maintained over many weeks. These data provide evidence for stable representations of visual cues in RSC that are spatially selective. These may provide sensory data to contribute to the formation of memories of spatial information

Inverse Vulcanization of Norbornenylsilanes: Soluble Polymers with Controllable Molecular Properties via Siloxane Bonds

The inverse vulcanization produces high sulfur content polymers from alkenes and elemental sulfur. Control over properties such as the molar mass or the solubility of polymers is not well established, and existing strategies lack predictability or require large variations of the composition. Systematic design principles are sought to allow for a targeted design of materials. Herein, we report on the inverse vulcanization of norbornenylsilanes (NBS), with a different number of hydrolysable groups at the silicon atom. Inverse vulcanization of mixtures of NBS followed by polycondensation yielded soluble high sulfur content copolymers (50 wt % S) with controllable weight average molar mass (M$_{W}$), polydispersity (Đ), glass transition temperature (TG), or zero-shear viscosity (η$_{0}$). Polycondensation was conducted in the melt with HCl as a catalyst, abolishing the need for a solvent. Purification by precipitation afforded polymers with a greatly reduced amount of low molar mass species

FULFIL Trial: Once-Daily Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease

RATIONALE: Randomized data comparing triple therapy with dual inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) are limited. OBJECTIVES: We compared the effects of once-daily triple therapy on lung function and health-related quality of life with twice-daily ICS/LABA therapy. METHODS: FULFIL was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticasone furoate/umeclidinium/vilanterol 100 μg/62.5 μg/25 μg; ELLIPTA(®) inhaler) with twice-daily ICS/LABA therapy (budesonide/formoterol 400 μg/12 μg; Turbuhaler(®)). A patient subgroup remained on blinded treatment for up to 52 weeks. Co-primary endpoints were change from baseline in trough forced expiratory volume in 1 second (FEV1) and in St George's Respiratory Questionnaire (SGRQ) Total score, at Week 24. MEASUREMENTS AND MAIN RESULTS: In the intent-to-treat population (N = 1,810) at Week 24 for triple therapy (n = 911) and ICS/LABA therapy (n = 899): mean change from baseline in FEV1 was 142 mL (95% confidence interval [CI], 126,158) and -29 mL (95% CI, -46,-13), respectively; mean change from baseline SGRQ was -6.6 units (95% CI, -7.4,-5.7) and -4.3 units (95% CI, -5.2,-3.4), respectively. For both endpoints, the between-group differences were statistically significant (P < 0.001). There was a statistically significant reduction in moderate/severe exacerbation rate with triple versus ICS/LABA therapy (35% reduction, 95% CI, 14,51; P = 0.002). The safety profile of triple therapy reflected the known profiles of the components. CONCLUSIONS: These results support the benefits of single inhaler triple therapy compared with ICS/LABA therapy, in patients with advanced COPD. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02345161