Functional Properties of Cortical Feedback Projections to the Olfactory Bulb

SummarySensory perception is not a simple feed-forward process, and higher brain areas can actively modulate information processing in “lower” areas. We used optogenetic methods to examine how cortical feedback projections affect circuits in the first olfactory processing stage, the olfactory bulb. Selective activation of back projections from the anterior olfactory nucleus/cortex (AON) revealed functional glutamatergic synaptic connections on several types of bulbar interneurons. Unexpectedly, AON axons also directly depolarized mitral cells (MCs), enough to elicit spikes reliably in a time window of a few milliseconds. MCs received strong disynaptic inhibition, a third of which arises in the glomerular layer. Activating feedback axons in vivo suppressed spontaneous as well as odor-evoked activity of MCs, sometimes preceded by a temporally precise increase in firing probability. Our study indicates that cortical feedback can shape the activity of bulbar output neurons by enabling precisely timed spikes and enforcing broad inhibition to suppress background activity

Stabilisation of beta and gamma oscillation frequency in the mammalian olfactory bulb

International audienceThe dynamics of the mammalian olfactory bulb (OB) is characterized by local field potential (LFP) oscillations either slow, in the theta range (2-10Hz, tightly linked to the respiratory rhythm), or fast, in the beta (15-30Hz) or gamma (40-90Hz) range. These fast oscillations are known to be modulated by odorant features and animal experience or state, but both their mechanisms and implication in coding are still not well understood. In this study, we used a double canulation protocol to impose artificial breathing rhythms to anesthetized rats while recording the LFP in the OB. We observed that despite the changes in the input air flow parameters (frequency or flow rate), the main characteristics of fast oscillations (duration, frequency or amplitude) were merely constant. We thus made the hypothesis that fast beta and gamma oscillations dynamics are entirely determined by the OB network properties and that external stimulation was only able put the network in a state which permits the generation of one or the other oscillations (they are never present simultaneously)

The impact of chorionicity on pregnancy outcome and neurodevelopment at 2 years old among twins born preterm: the EPIPAGE-2 cohort study

OBJECTIVE To compare the short‐ and mid‐term outcomes of preterm twins by chorionicity of pregnancy. DESIGN Prospective nationwide population‐based EPIPAGE‐2 cohort study. SETTING 546 maternity units in France, between March and December 2011. POPULATION A total of 1700 twin neonates born between 24 and 34 weeks of gestation. METHODS The association of chorionicity with outcomes was analysed using multivariate regression models. MAIN OUTCOME MEASURES First, survival at 2‐year corrected age with or without neurosensory impairment, and second, perinatal, short‐, and mid‐term outcomes (survival at discharge, survival at discharge without severe morbidity) were described and compared by chorionicity. RESULTS In the EPIPAGE 2 cohort, 1700 preterm births were included (850 twin pregnancies). In all, 1220 (71.8%) were from dichorionic (DC) pregnancies and 480 from monochorionic (MC) pregnancies. MC pregnancies had three times more medical terminations than DC pregnancies (1.67 versus 0.51%, P < 0.001), whereas there were three times more stillbirths in MC than in DC pregnancies (10.09 versus 3.78%, P < 0.001). Both twins were alive at birth in 86.6% of DC pregnancies compared with 80.0% among MC pregnancies (P = 0.008). No significant difference according to chorionicity was found regarding neonatal deaths and morbidities. Likewise, for children born earlier than 32 weeks, the 2‐year follow‐up neurodevelopmental results were not significantly different between DC and MC twins. CONCLUSIONS This study confirms that MC pregnancies have a higher risk of adverse outcomes. However, the outcomes among preterm twins admitted to neonatal intensive care units are similar irrespective of chorionicity

‘Care Co-ordinator In My Pocket’. A Feasibility study of Mobile-Assessment and Therapy for Psychosis (TechCare).

Objectives: The research aimed to examine the acceptability and feasibility of a mobile phone Application (App) based intervention ‘TechCare’, for individuals with psychosis in the North West of England. The main objectives were to determine whether appropriate individuals could be identified and recruited to the study and whether the TechCare App would be an acceptable intervention for individuals with psychosis. Methods: This was a mixed methods feasibility study, consisting of a test-run and feasibility evaluation of the TechCare App intervention. Setting: Early Intervention Services for psychosis, within an NHS Trusts in the North West of England. Participants: Sixteen participants (Test-run n=4, feasibility study n=12) aged between 18-65, recruited from the East, Central and North Lancashire Early Intervention Service (EIS). Intervention: A 6-week intervention, with the TechCare App assessing participants’ symptoms and responses in real-time and providing a personalised guided self-help based psychological intervention based on the principles of CBT. Results: A total of 83.33% (n=10) of participants completed the 6-week feasibility study, with 70% of completers achieving the set compliance threshold of ≥33% engagement with the TechCare App system. Analysis of the qualitative data suggested that participants held the view that the TechCare was both an acceptable and feasible means of delivering interventions in real-time. Conclusion: Innovative digital clinical technologies such as the TechCare App may have the potential to increase access to psychological interventions, reduce health inequality, and promote self-management with a real-time intervention, through enabling access to mental health resources in a stigma-free, evidence-based, and time-independent manner. Trial registration number: ClinicalTrials.gov Identifier: NCT0243961

TechCare: Mobile-assessment and therapy for psychosis: An intervention for clients within the early intervention service

In the UK, mental illness is a major source of disease burden costing in the region of £105 billion pounds. mHealth is a novel and emerging field in psychiatric and psychological care for the treatment of mental health difficulties such as psychosis

IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome

Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species

Nr2e3 is a Genetic Modifier That Rescues Retinal Degeneration and Promotes Homeostasis in Multiple Models of Retinitis Pigmentosa

Recent advances in viral vector engineering, as well as an increased understanding of the cellular and molecular mechanism of retinal diseases, have led to the development of novel gene therapy approaches. Furthermore, ease of accessibility and ocular immune privilege makes the retina an ideal target for gene therapies. In this study, the nuclear hormone receptor gene Nr2e3 was evaluated for efficacy as broad-spectrum therapy to attenuate early to intermediate stages of retinal degeneration in five unique mouse models of retinitis pigmentosa (RP). RP is a group of heterogenic inherited retinal diseases associated with over 150 gene mutations, affecting over 1.5 million individuals worldwide. RP varies in age of onset, severity, and rate of progression. In addition, ~40% of RP patients cannot be genetically diagnosed, confounding the ability to develop personalized RP therapies. Remarkably, Nr2e3 administered therapy resulted in reduced retinal degeneration as observed by increase in photoreceptor cells, improved electroretinogram, and a dramatic molecular reset of key transcription factors and associated gene networks. These therapeutic effects improved retinal homeostasis in diseased tissue. Results of this study provide evidence that Nr2e3 can serve as a broad-spectrum therapy to treat multiple forms of RP

Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014

In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: “Makona”, Middle Africa: “Lomela”) and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures