Cueing involuntary memory.

We raise two points about cues, which complicate Barzykowski and Moulin's attempt at a unified model of memory retrieval. First, cues operate differently in voluntary and involuntary contexts. Second, voluntary and involuntary memory can be interconnected, as in cases of chaining.

NG2-Glia, a New Player in Energy Balance.

There is increasing evidence that glia act not only as neuronal support cells, but that they can also influence physiological outcomes via effects on neural signalling. The role of NG2-glia in this regard is especially enigmatic, as they are known to interact with neural circuits but their precise functions other than as oligodendrocyte progenitor cells remain elusive. Here, we summarise recent evidence suggesting that NG2-glia play a role in the maintenance of energy homeostasis, most notably via the support of leptin-sensing neural circuits. We also discuss the potential clinical implication of these findings specifically in the context of cranial radiation therapy.

Confabulation and epistemic authority.

Mahr & Csibra (M&C) claim that episodic remembering's autonoetic character serves as an indicator of epistemic authority. This proposal is difficult to reconcile with the existence of confabulation errors - where participants fabricate memories of experiences that never happened to them. Making confabulation errors damages one's epistemic authority, but these false memories have an autonoetic character.

Parent-child conversations about literacy: a longitudinal, observational study.

Conversations about literacy-related matters with parents can help prepare children for formal literacy instruction. We studied these conversations using data gathered from fifty-six US families as they engaged in daily activities at home. Analyzing conversations when children were aged 1;10, 2;6, 3;6, and 4;2, we found that explicit talk about the elements and processes of reading and writing occurred even when children were less than two years old and became more common as children grew older. The majority of literacy-related conversations included talk about alphabet letters. Literacy-related conversations occurred in a variety of contexts, not only book-reading. There were few differences as a function of family socioeconomic status in the proportion of utterances during the sessions that occurred in literacy-related conversations. At older ages, however, children in families of lower socioeconomic status bore more of the conversational burden than children in families of higher status.

Parents' Talk About Letters With Their Young Children.

A literacy-related activity that occurs in children's homes-talk about letters in everyday conversations-was examined using data from 50 children who were visited every 4 months between 14 and 50 months. Parents talked about some letters, including those that are common in English words and the first letter of their children's names, especially often. Parents' focus on the child's initial was especially strong in families of higher socioeconomic status, and the extent to which parents talked about the child's initial during the later sessions of the study was related to the children's kindergarten reading skill. Conversations that included the child's initial were longer than those that did not, and parents presented a variety of information about this letter.

Extensive regenerative plasticity among adult NG2-glia populations is exclusively based on self-renewal.

NG2-glia are known to proliferate in the adult brain, however the extent of their mitotic and regenerative capacity and particularly their adult origin is uncertain. By employing a paradigm of mitotic blockade in conjunction with genetic fate tracing we demonstrate that intracerebroventricular mitotic blocker infusion leads to wide-spread and complete ablation of NG2-glial cells in the hypothalamus and other periventricular brain regions. However, despite the extensive glia loss, parenchymal NG2-glia coverage is fully restored to pretreatment levels within two weeks. We further reveal that in response to mitotic blocker treatment, NG2-glia bordering the ablated territories start to express the stem cell marker nestin, divide and migrate to replace the lost cells. Importantly, the migration front of repopulating NG2-glia invariably proceeds from the distal parenchyma towards the ventricles, ruling out contributions of the subventricular zone neurogenic niche or the corresponding area of the third ventricle as source of new NG2-glia. NG2-CreER-based fate tracing further substantiates that NG2-glia which have been spared from mitotic blockade are the sole source of regenerating NG2-glia. Collectively, our data reveals that all adult NG2-glia retain the ability to divide and that they are capable of fully restoring parenchymal NG2-glia coverage after wide-spread NG2 cell loss, indicating complete self-sufficiency in maintaining NG2-glia population levels in the adult brain.

The 21st century engram.

The search for the engram-the neural mechanism of memory-has been a guiding research project for neuroscience since its emergence as a distinct scientific field. Recent developments in the tools and techniques available for investigating the mechanisms of memory have allowed researchers to proclaimed the search is over. While there is ongoing debate about the justification for that claim, renewed interest in the engram is clear. This attention highlights the impoverished status of the engram concept. As research accelerates, the simple characterization of the engram as an enduring physical change is stretched thin. Now that the engram commitment has been made more explicit, it must also be made more precise. If the project of 20th century neurobiology was finding the engram, the project of the 21st must be supplying a richer account of what's been found. This paper sketches a history of the engram, and a way forward. This article is categorized under: Philosophy > Foundations of Cognitive Science.

Implementation of a risk-stratified, guideline-based clinical pathway of care to improve health outcomes following whiplash injury (Whiplash ImPaCT): a multicentre, randomized, controlled trial.

ABSTRACT: Current pathways of care for whiplash follow a "stepped care model," result in modest treatment outcomes and fail to offer efficient management solutions. This study aimed to evaluate the effectiveness of a risk-stratified clinical pathway of care (CPC) compared with usual care (UC) in people with acute whiplash. We conducted a multicentre, 2-arm, parallel, randomised, controlled trial in primary care in Australia. Participants with acute whiplash (n = 216) were stratified for risk of a poor outcome (low vs medium/high risk) and randomised using concealed allocation to either the CPC or UC. In the CPC group, low-risk participants received guideline-based advice and exercise supported by an online resource, and medium-risk/high-risk participants were referred to a whiplash specialist who assessed modifiable risk factors and then determined further care. The UC group received care from their primary healthcare provider who had no knowledge of risk status. Primary outcomes were neck disability index (NDI) and Global Rating of Change (GRC) at 3 months. Analysis blinded to group used intention-to-treat and linear mixed models. There was no difference between the groups for the NDI (mean difference [MD] [95% confidence interval (CI)] -2.34 [-7.44 to 2.76]) or GRC (MD 95% CI 0.08 [-0.55 to 0.70]) at 3 months. Baseline risk category did not modify the effect of treatment. No adverse events were reported. Risk-stratified care for acute whiplash did not improve patient outcomes, and implementation of this CPC in its current form is not recommended.

Loss of Function of the Neural Cell Adhesion Molecule NrCAM Regulates Differentiation, Proliferation and Neurogenesis in Early Postnatal Hypothalamic Tanycytes.

Hypothalamic tanycytes are neural stem and progenitor cells, but little is known of how they are regulated. Here we provide evidence that the cell adhesion molecule, NrCAM, regulates tanycytes in the adult niche. NrCAM is strongly expressed in adult mouse tanycytes. Immunohistochemical and in situ hybridization analysis revealed that NrCAM loss of function leads to both a reduced number of tanycytes and reduced expression of tanycyte-specific cell markers, along with a small reduction in tyrosine hydroxylase-positive arcuate neurons. Similar analyses of NrCAM mutants at E16 identify few changes in gene expression or cell composition, indicating that NrCAM regulates tanycytes, rather than early embryonic hypothalamic development. Neurosphere and organotypic assays support the idea that NrCAM governs cellular homeostasis. Single-cell RNA sequencing (scRNA-Seq) shows that tanycyte-specific genes, including a number that are implicated in thyroid hormone metabolism, show reduced expression in the mutant mouse. However, the mild tanycyte depletion and loss of markers observed in NrCAM-deficient mice were associated with only a subtle metabolic phenotype.

Development and use of mobile messaging for individuals with musculoskeletal pain conditions: a scoping review protocol.

INTRODUCTION: Previous reviews of mobile messaging for individuals with musculoskeletal pain have shown positive effects on pain and disability. However, the configuration of digital content, method of presentation and interaction, dose and frequency needed for optimal results remain unclear. Patient preferences concerning such systems are also unclear. Addressing these knowledge gaps, incorporating evidence from both experimental and observational studies, may be useful to understand the extent of the relevant literature, and to influence the design and outcomes of future messaging systems. We aim to map information that could be influential in the design of future mobile messaging systems for individuals with musculoskeletal pain conditions, and to summarise the findings of efficacy, effectiveness, and economics derived from both experimental and observational studies. METHODS AND ANALYSIS: We will include studies describing the development and/or use of mobile messaging to support adults (≥18 years) with acute or chronic musculoskeletal pain. We will exclude digital health studies that lack a mobile messaging component, or those targeted at other health conditions unrelated to the bones, muscles and connective tissues, or involving surgical or patients with cancer, or studies involving solely healthy individuals. Our sources of information will be online databases and reference lists of relevant papers. We will include papers published in English in the last 10 years. Two pairs of independent reviewers will screen, select and extract the data, with any disagreements mediated by a third reviewer. We will report the results according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews checklist. We will synthesise the findings in a tabular format and provide a descriptive summary. ETHICS AND DISSEMINATION: Formal ethical approval is not required. We will disseminate the findings through publication in a peer-reviewed journal, relevant conferences, and relevant consumer forums. TRIAL REGISTRATION: Open Science Framework https://osf.io/8mzya; DOI: 10.17605/OSF.IO/8MZYA.

Leptin receptor-expressing pericytes mediate access of hypothalamic feeding centers to circulating leptin.

Knowledge of how leptin receptor (LepR) neurons of the mediobasal hypothalamus (MBH) access circulating leptin is still rudimentary. Employing intravital microscopy, we found that almost half of the blood-vessel-enwrapping pericytes in the MBH express LepR. Selective disruption of pericytic LepR led to increased food intake, increased fat mass, and loss of leptin-dependent signaling in nearby LepR neurons. When delivered intravenously, fluorescently tagged leptin accumulated at hypothalamic LepR pericytes, which was attenuated upon pericyte-specific LepR loss. Because a paracellular tracer was also preferentially retained at LepR pericytes, we pharmacologically targeted regulators of inter-endothelial junction tightness and found that they affect LepR neuronal signaling and food intake. Optical imaging in MBH slices revealed a long-lasting, tonic calcium increase in LepR pericytes in response to leptin, suggesting pericytic contraction and vessel constriction. Together, our data indicate that LepR pericytes facilitate localized, paracellular blood-brain barrier leaks, enabling MBH LepR neurons to access circulating leptin.

Adult NG2-Glia Are Required for Median Eminence-Mediated Leptin Sensing and Body Weight Control.

While leptin is a well-known regulator of body fat mass, it remains unclear how circulating leptin is sensed centrally to maintain energy homeostasis. Here we show that genetic and pharmacological ablation of adult NG2-glia (also known as oligodendrocyte precursors), but not microglia, leads to primary leptin resistance and obesity in mice. We reveal that NG2-glia contact the dendritic processes of arcuate nucleus leptin receptor (LepR) neurons in the median eminence (ME) and that these processes degenerate upon NG2-glia elimination, which explains the consequential attenuation of these neurons' molecular and electrical responses to leptin. Our data therefore indicate that LepR dendrites in the ME represent the principal conduits of leptin's anorexigenic action and that NG2-glia are essential for their maintenance. Given that ME-directed X-irradiation confirmed the pharmacological and genetically mediated ablation effects on body weight, our findings provide a rationale for the known obesity risk associated with cranial radiation therapy.

Letter Knowledge in Parent-Child Conversations.

Learning about letters is an important component of emergent literacy. We explored the possibility that parent speech provides information about letters, and also that children's speech reflects their own letter knowledge. By studying conversations transcribed in CHILDES (MacWhinney, 2000) between parents and children aged one to five, we found that alphabetic order influenced use of individual letters and letter sequences. The frequency of letters in children's books influenced parent utterances throughout the age range studied, but children's utterances only after age two. Conversations emphasized some literacy-relevant features of letters, such as their shapes and association with words, but not letters' sounds. Describing these patterns and how they change over the preschool years offers important insight into the home literacy environment.

Letter knowledge in parent-child conversations: differences between families differing in socio-economic status.

When formal literacy instruction begins, around the age of 5 or 6, children from families low in socioeconomic status (SES) tend to be less prepared than children from families of higher SES. The goal of our study is to explore one route through which SES may influence children's early literacy skills: informal conversations about letters. The study builds on previous studies (Robins and Treiman, 2009; Robins et al., 2012, 2014) of parent-child conversations that show how U. S. parents and their young children talk about writing and provide preliminary evidence about similarities and differences in parent-child conversations as a function of SES. Focusing on parents and children aged three to five, we conducted five separate analyses of these conversations, asking whether and how family SES influences the previously established patterns. Although we found talk about letters in both upper and lower SES families, there were differences in the nature of these conversations. The proportion of letter talk utterances that were questions was lower in lower SES families and, of all the letter names that lower SES families talked about, more of them were uttered in isolation rather than in sequences. Lower SES families were especially likely to associate letters with the child's name, and they placed more emphasis on sequences in alphabetic order. We found no SES differences in the factors that influenced use of particular letter names (monograms), but there were SES differences in two-letter sequences (digrams). Focusing on the alphabet and on associations between the child's name and the letters within it may help to interest the child in literacy activities, but they many not be very informative about the relationship between letters and words in general. Understanding the patterns in parent-child conversations about letters is an important first step for exploring their contribution to children's early literacy skills and school readiness.

Evidence for NG2-glia derived, adult-born functional neurons in the hypothalamus.

Accumulating evidence suggests that the adult murine hypothalamus, a control site of several fundamental homeostatic processes, has neurogenic capacity. Correspondingly, the adult hypothalamus exhibits considerable cell proliferation that is ongoing even in the absence of external stimuli, and some of the newborn cells have been shown to mature into cells that express neuronal fate markers. However, the identity and characteristics of proliferating cells within the hypothalamic parenchyma have yet to be thoroughly investigated. Here we show that a subset of NG2-glia distributed throughout the mediobasal hypothalamus are proliferative and express the stem cell marker Sox2. We tracked the constitutive differentiation of hypothalamic NG2-glia by employing genetic fate mapping based on inducible Cre recombinase expression under the control of the NG2 promoter, demonstrating that adult hypothalamic NG2-glia give rise to substantial numbers of APC+ oligodendrocytes and a smaller population of HuC/D+ or NeuN+ neurons. Labelling with the cell proliferation marker BrdU confirmed that some NG2-derived neurons have proliferated shortly before differentiation. Furthermore, patch-clamp electrophysiology revealed that some NG2-derived cells display an immature neuronal phenotype and appear to receive synaptic input indicative of their electrical integration in local hypothalamic circuits. Together, our studies show that hypothalamic NG2-glia are able to take on neuronal fates and mature into functional neurons, indicating that NG2-glia contribute to the neurogenic capacity of the adult hypothalamus.

Parent-Child Conversations About Letters and Pictures.

Learning about letters, and how they differ from pictures, is one important aspect of a young child's print awareness. To test the hypothesis that parent speech provides children with information about these differences, we studied parent-child conversations in CHILDES (MacWhinney, 2000). We found that parents talk to their young children about letters, differentiating them from pictures, by 1-2 years of age and that some of these conversational patterns change across the preschool years in ways that emphasize important features of letters, such as their shape. We also found that children talk about letters and pictures in distinct ways, suggesting an implicit understanding of some of the differences between letters and pictures at an early age. Some differences in parent-child conversations about letters were found as a function of socioeconomic status: Lower SES families appeared to focus more on alphabetic order than higher SES families. The general letter knowledge expressed in these conversations suggests that everyday interactions are an important component of the home literacy environment and that they differ, in some respects, as a function of child age and family background.

The mating sociometer: a regulatory mechanism for mating aspirations.

Two studies (Ns = 80 and 108) tested hypotheses derived from Kirkpatrick and Ellis's (2001) extension and application of sociometer theory to mating aspirations. Experiences of social rejection-acceptance by attractive opposite-sex confederates were experimentally manipulated, and the impact of these manipulations on self-esteem, mating aspirations, and friendship aspirations was assessed. Results indicated that social rejection-acceptance by members of the opposite sex altered mating aspirations; that the causal link between social rejection-acceptance and mating aspirations was mediated by changes in state self-esteem; and that the impact of social rejection-acceptance by members of opposite sex was specific to mating aspirations and did not generalize to levels of aspiration in approaching potential same-sex friendships. This research supports a conceptualization of a domain-specific mating sociometer, which functions to calibrate mating aspirations in response to experiences of romantic rejection and acceptance.

Talking About Writing: What We Can Learn from Conversations between Parents and Their Young Children.

In six analyses using CHILDES (MacWhinney, 2000), we explored whether and how parents and their 1.5 to 5-year-old children talk about writing. Parent speech might include information about the similarity between print and speech and about the difference between writing and drawing. Parents could convey similarity between print and speech by using the words say, name, and word to refer to both spoken and written language. Parents could differentiate writing and drawing by making syntactic and semantic distinctions in their discussion of the two symbol systems. Our results indicate that parent speech includes these types of information. However, young children themselves sometimes confuse writing and drawing in their speech.