Extinction and Retrieval + Extinction of Conditioned Fear Differentially Activate Medial Prefrontal Cortex and Amygdala in Rats

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window (termed retrieval+extinction) attenuates fear responding and prevents the return of fear in Pavlovian fear conditioning (Monfils et al., 2009). To date, the mechanisms that explain the different behavioral outcomes between standard extinction and retrieval+extinction remain poorly understood. Here we sought to examine the differential temporal engagement of specific neural systems by these 2 approaches using Arc catFISH (cellular compartment analysis of temporal activity using fluorescence in situ hybridization). Our results demonstrate that extinction and retrieval+extinction lead to differential patterns of expression, suggesting that they engage different networks. These findings provide insight into the neural mechanisms that allow extinction during reconsolidation to prevent the return of fear in rats

Extinction, applied after retrieval of auditory fear memory, selectively increases zinc-finger protein 268 and phosphorylated ribosomal protein S6 expression in prefrontal cortex and lateral amygdala

Abstract Retrieval of consolidated memories induces a labile phase during which memory can be disrupted or updated through a reconsolidation process. A central component of behavioral updating during reconsolidation using a retrieval–extinction manipulation (Ret + Ext) is the synaptic removal of a calcium-permeable-α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (CP-AMPARs) in the lateral amygdala—a metabotropic GluR1 receptor (mGluR1) dependent mechanism. In the present study, we investigate the effect of Ret + Ext on the expression of molecular markers that could play a role in the reconsolidation process. Specifically, we tested the effects of Ret + Ext on the global expression of zinc-finger 268 protein (Zif268), a marker previously found to be implicated in memory reconsolidation, to confirm its occurrence after retrieval (Ret) and Ret + Ext. We also evaluated the global expression of phosphorylated ribosomal protein S6 (rpS6P), here proposed as a marker of the mGluR1-mediated memory process induced by Ret + Ext. The expression of both markers (zif268, rpS6P) was assessed by immunolocalization in prelimbic cortex (PRL), infralimbic cortex (IL), ventral subdivision of the lateral amygdala (LA) and hippocampus CA1 (CA1) in fear-conditioned rats. Our results showed that retrieval and Ret + Ext, but not extinction alone, increased Zif268 expression in prefrontal cortex and lateral amygdala. Ret + Ext, but not retrieval, retrieval followed by context exposure or extinction alone, increased the expression of rpS6P in prefrontal cortex and LA. In summary, (i) Zif268 increased after retrieval confirming that reconsolidation is engaged in our conditions, (ii) Zif268 increased after Ret + Ext confirming that it does not simply reflect an extinction or reconsolidation disruption (Zif268 level of expression should be lower in both cases) and (iii) rpS6P increased after Ret + Ext, but not after extinction, suggesting, as expected, a potential mGluR1 mediated molecular mechanism specific for Ret + Ext. Together with the Zif268 increase, our results suggest that the Ret + Ext induced memory process is more similar to reconsolidation updating than extinction facilitation

The Southern Ocean deep mixing band emerges from a competition between winter buoyancy loss and upper stratification strength

The Southern Ocean hosts a winter deep mixing band (DMB) near the Antarctic Circumpolar Current's (ACC) northern boundary, playing a pivotal role in Subantarctic Mode Water formation. Here, we investigate what controls the presence and geographical extent of the DMB. Using observational data, we construct seasonal climatologies of surface buoyancy fluxes, Ekman buoyancy transport, and upper stratification. The strength of the upper-ocean stratification is determined using the columnar buoyancy index, defined as the buoyancy input necessary to produce a 250 m deep mixed layer. It is found that the DMB lies precisely where the autumn–winter buoyancy loss exceeds the columnar buoyancy found in late summer. The buoyancy loss decreases towards the south, while in the north the stratification is too strong to produce deep mixed layers. Although this threshold is also crossed in the Agulhas Current and East Australian Current regions, advection of buoyancy is able to stabilise the stratification. The Ekman buoyancy transport has a secondary impact on the DMB extent due to the compensating effects of temperature and salinity transports on buoyancy. Changes in surface temperature drive spatial variations in the thermal expansion coefficient (TEC). These TEC variations are necessary to explain the limited meridional extent of the DMB. We demonstrate this by comparing buoyancy budgets derived using varying TEC values with those derived using a constant TEC value. Reduced TEC in colder waters leads to decreased winter buoyancy loss south of the DMB, yet substantial heat loss persists. Lower TEC values also weaken the effect of temperature stratification, partially compensating for the effect of buoyancy loss damping. TEC modulation impacts both the DMB characteristics and its meridional extent.</p

Mycobacteriophage-antibiotic therapy promotes enhanced clearance of drug-resistant Mycobacterium abscessus.

Infection by multidrug-resistant Mycobacterium abscessus is increasingly prevalent in cystic fibrosis (CF) patients, leaving clinicians with few therapeutic options. A compassionate study showed the clinical improvement of a CF patient with a disseminated M. abscessus (GD01) infection, following injection of a phage cocktail, including phage Muddy. Broadening the use of phage therapy in patients as a potential antibacterial alternative necessitates the development of biological models to improve the reliability and successful prediction of phage therapy in the clinic. Herein, we demonstrate that Muddy very efficiently lyses GD01 in vitro, an effect substantially increased with standard drugs. Remarkably, this cooperative activity was retained in an M. abscessus model of infection in CFTR-depleted zebrafish, associated with a striking increase in larval survival and reduction in pathological signs. The activity of Muddy was lost in macrophage-ablated larvae, suggesting that successful phage therapy relies on functional innate immunity. CFTR-depleted zebrafish represent a practical model to rapidly assess phage treatment efficacy against M. abscessus isolates, allowing the identification of drug combinations accompanying phage therapy and treatment prediction in patients. This article has an associated First Person interview with the first author of the paper

On cabbeling and thermobaricity in the surface mixed layer

The surface mixed layer (ML) governs atmosphere–ocean fluxes, and thereby affects Earth’s climate. Accurate representation of ML processes in ocean models remains a challenge, however. The O(100) m deep ML exhibits substantial horizontal thermohaline gradients, despite being near-homogenous vertically, making it an ideal location for processes that result from the nonlinearity of the equation of state, such as cabbeling and thermobaricity. Traditional approaches to investigate these processes focus on their roles in interior water-mass transformation and are ill suited to examine their influence on the ML. However, given the climatic significance of the ML, quantifying the extent to which cabbeling and thermobaricity influence the ML density field offers insight into improving ML representations in ocean models. A recent simplified equation of state of seawater allows the local effects of cabbeling and thermobaric processes in the ML to be expressed analytically as functions of the local temperature gradient and ML depth. These simplified expressions are used to estimate the extent to which cabbeling and thermobaricity contribute to local ML density differences. These estimates compare well with values calculated directly using the complete nonlinear equation of state. Cabbeling and thermobaricity predominantly influence the ML density field poleward of 30°. Mixed layer thermobaricity is basin-scale and winter intensified, while ML cabbeling is perennial and localized to intense, zonally coherent regions associated with strong temperature fronts, such as the Antarctic Circumpolar Current and the Kuroshio and Gulf Stream Extensions. For latitudes between 40° and 50° in both hemispheres, the zonally averaged effects of ML cabbeling and ML thermobaricity can contribute on the order of 10% of the local ML density difference.K.D.S. was supported by Australian Research Council Grant DP140103706; T.W.N.H. was supported by National Science Foundation Grants 1338814 and 1536554, and A.M.H. was supported by Australian Research Council Grant CE11000102

Increasing phylogenetic stochasticity at high elevations on summits across a remote North American wilderness

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/1/ajb21328-sup-0002-AppendixS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/2/ajb21328-sup-0003-AppendixS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/3/ajb21328-sup-0004-AppendixS4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/4/ajb21328.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/5/ajb21328-sup-0009-AppendixS9.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/6/ajb21328-sup-0005-AppendixS5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/7/ajb21328-sup-0007-AppendixS7.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/8/ajb21328-sup-0006-AppendixS6.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/9/ajb21328-sup-0008-AppendixS8.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/10/ajb21328_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/11/ajb21328-sup-0001-AppendixS1.pd

Trackly:A Customisable and Pictorial Self-Tracking App to Support Agency in Multiple Sclerosis Self-Care

Self-tracking is an important part of self-care. However, predefined self-tracking approaches can impede people's agency in managing their health. We investigated a customisable and pictorial self-tracking approach in multiple sclerosis self-management by implementing and conducting a field study of Trackly: a prototype app that supports people in defining and colouring pictorial trackers, such as body shapes. We found that participants utilised the elements of Trackly designed to support agentive behaviour: they defined personally meaningful tracking parameters in their own words, and particularly valued being able to flexibly colour in and make sense of their pictorial trackers. Having been able to support their individual self-care intentions with Trackly, participants reported a spectrum of interrelated experiences of agency, including a sense of ownership, identity, self-awareness, mindfulness, and control. Our findings demonstrate the importance of supporting people's individual needs and creative capacities to foster mindful and personally meaningful engagement with health and wellbeing data

Colloquium: Mechanical formalisms for tissue dynamics

The understanding of morphogenesis in living organisms has been renewed by tremendous progressin experimental techniques that provide access to cell-scale, quantitative information both on theshapes of cells within tissues and on the genes being expressed. This information suggests that ourunderstanding of the respective contributions of gene expression and mechanics, and of their crucialentanglement, will soon leap forward. Biomechanics increasingly benefits from models, which assistthe design and interpretation of experiments, point out the main ingredients and assumptions, andultimately lead to predictions. The newly accessible local information thus calls for a reflectionon how to select suitable classes of mechanical models. We review both mechanical ingredientssuggested by the current knowledge of tissue behaviour, and modelling methods that can helpgenerate a rheological diagram or a constitutive equation. We distinguish cell scale ("intra-cell")and tissue scale ("inter-cell") contributions. We recall the mathematical framework developpedfor continuum materials and explain how to transform a constitutive equation into a set of partialdifferential equations amenable to numerical resolution. We show that when plastic behaviour isrelevant, the dissipation function formalism appears appropriate to generate constitutive equations;its variational nature facilitates numerical implementation, and we discuss adaptations needed in thecase of large deformations. The present article gathers theoretical methods that can readily enhancethe significance of the data to be extracted from recent or future high throughput biomechanicalexperiments.Comment: 33 pages, 20 figures. This version (26 Sept. 2015) contains a few corrections to the published version, all in Appendix D.2 devoted to large deformation