N-cadherin facilitates trigeminal sensory neuron outgrowth and target tissue innervation.

During embryonic development, diverse cell types coordinate to form functionally complex tissues. Exemplifying this process, the trigeminal ganglion emerges from the condensation of two distinct precursor cell populations, cranial placodes and neural crest, with neuronal differentiation of the former preceding the latter. While the dual origin of the trigeminal ganglion has been understood for decades, the molecules orchestrating formation of the trigeminal ganglion from these precursors remain relatively obscure. Initial assembly of the trigeminal ganglion is mediated by cell adhesion molecules, including neural cadherin (N-cadherin), which is required by placodal neurons to properly condense with other neurons and neural crest cells. Whether N-cadherin is required for later growth and target innervation by trigeminal ganglion neurons, however, is unknown. To this end, we depleted N-cadherin from chick trigeminal placode cells and uncovered decreases in trigeminal ganglion size, nerve growth, and target innervation in vivo at later developmental stages. Furthermore, blocking N-cadherin-mediated adhesion prevented axon extension in some placode-derived trigeminal neurons in vitro . This indicates the existence of neuronal subtypes that may have unique requirements for N-cadherin for outgrowth, and points to this subset of placodal neurons as potential pioneers that serve as templates for additional axon outgrowth. Neurite complexity was also decreased in neural crest-derived neurons in vitro in response to N-cadherin knockdown in placode cells. Collectively, these findings reveal persistent cell autonomous and non-cell autonomous functions for N-cadherin, thus highlighting the critical role of N-cadherin in mediating reciprocal interactions between neural crest and placode neuronal derivatives during trigeminal ganglion development. Significance Statement: Our findings are significant because they demonstrate how neurons derived from two distinct cell populations, neural crest and placode cells, coordinate the outgrowth of their axons in time and space to generate the trigeminal ganglion using the cell adhesion molecule N-cadherin. Notably, our results provide evidence for the existence of subpopulations of neurons within the trigeminal ganglion that differentially require N-cadherin to facilitate axon outgrowth, and hint at the possibility that trigeminal pioneer neurons are derived from placode cells while followers arise from both placode and neural crest cells. These studies provide new insight into trigeminal gangliogenesis that will likely be translatable to other cranial ganglia and vertebrate species.

Loss of Elp1 disrupts trigeminal ganglion neurodevelopment in a model of familial dysautonomia.

Familial dysautonomia (FD) is a sensory and autonomic neuropathy caused by mutations in elongator complex protein 1 (ELP1). FD patients have small trigeminal nerves and impaired facial pain and temperature perception. These signals are relayed by nociceptive neurons in the trigeminal ganglion, a structure that is composed of both neural crest- and placode-derived cells. Mice lacking Elp1 in neural crest derivatives ('Elp1 CKO') are born with small trigeminal ganglia, suggesting Elp1 is important for trigeminal ganglion development, yet the function of Elp1 in this context is unknown. We demonstrate that Elp1, expressed in both neural crest- and placode-derived neurons, is not required for initial trigeminal ganglion formation. However, Elp1 CKO trigeminal neurons exhibit abnormal axon outgrowth and deficient target innervation. Developing nociceptors expressing the receptor TrkA undergo early apoptosis in Elp1 CKO, while TrkB- and TrkC-expressing neurons are spared, indicating Elp1 supports the target innervation and survival of trigeminal nociceptors. Furthermore, we demonstrate that specific TrkA deficits in the Elp1 CKO trigeminal ganglion reflect the neural crest lineage of most TrkA neurons versus the placodal lineage of most TrkB and TrkC neurons. Altogether, these findings explain defects in cranial gangliogenesis that may lead to loss of facial pain and temperature sensation in FD.

Indigenous Gambling and Problem Gambling in Canada.

The present study provides a profile of Canadian Indigenous gambling and problem gambling using the 2018 Canadian Community Health Survey (CCHS) (n = 23,952 adults; 1,324 Indigenous) and an online panel survey of 10,199 gamblers (n = 589 Indigenous). The relative popularity of different types of gambling was similar between Indigenous and non-Indigenous samples. However, there was higher Indigenous participation in electronic gambling machines (EGMs), bingo, instant lotteries, overall gambling and a higher rate of problem gambling (2.0% versus 0.5%). Variables predictive of Indigenous problem gambling were EGM participation, gambling fallacies, having a mental or substance use disorder, sports betting, and male gender. Compared to non-Indigenous problem gamblers, Indigenous problem gamblers had higher substance use and lower impulsivity. In general, variables predictive of Indigenous problem gambling were the same ones predictive of problem gambling in all populations, with elevated Indigenous problem gambling rates primarily being due to elevated rates of these generic risk factors. Many of these risk factors are modifiable. Particular consideration should be given to reducing the disproportionate concentration of EGMs in geographic areas having the highest concentration of Indigenous people and ameliorating the disadvantageous social conditions in this population that are conducive to mental health and substance use problems.

Gambling fallacies: Predicting problem gambling in a national sample.

Objective: The relationship between the level of gambling fallacy endorsement and type of gambler (nongambler, recreational gambler, at-risk gambler, and problem/pathological gambler) was assessed both concurrently and prospectively in a large national cohort of Canadian adults. Method: This cohort (n = 10,199 at baseline; 18-24 years, n = 481, 43% female; 25-34 years, n = 1,335, 62% female; 35-44 years, n = 1,543, 55% female, 45-54 years, n = 1,985, 58% female; 55-64 years, n = 2,459, 55% female; 65-74 years, n = 1,865, 44% female, 75+ years, n = 531, 43% female) was recruited from LEO, Leger Opinion's registered online panelists. The follow-up survey was completed by 55.9% of the cohort, 1 year after baseline. The full survey can be viewed at https://www.ucalgary.ca/research/national-gambling-study/. For the current study, scores on the Gambling Fallacies Measure, the Problem and Pathological Gambling Measure, Gambling Participation Instrument, and Impulsivity were analyzed. Results: There were three main findings. The first is that gambling fallacies are common in all categories of gamblers but somewhat more prevalent in problem and pathological gamblers. Second, the multivariate analysis determined that gambling fallacies are significant concurrent and prospective predictors of the problem/pathological gambling category, but not strong predictors relative to other variables. Third, problem gambling and heavier gambling involvement are also predictors of a future higher level of gambling fallacies. Conclusions: Collectively, these results show that gambling fallacies have some etiological relationship to problem gambling but are not the main cause of problem gambling and should not be the exclusive focus of problem gambling treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Predictors of gambling and problem gambling in Canada.

OBJECTIVES: The purpose of this study is to provide an updated profile of gamblers and problem gamblers in Canada and to identify characteristics most strongly associated with problem gambling. METHODS: An assessment of gambling participation and problem gambling was included in the 2018 Canadian Community Health Survey and administered to 23,952 individuals 18 years and older. Descriptive statistics provided a demographic profile for each type of gambling involvement as well as category of gambler (non-gambler, non-problem gambler, at-risk gambler, problem gambler). A logistic regression identified characteristics that best distinguished problem from non-problem gamblers. RESULTS: Gambling participation and problem gambling both varied as a function of gender, income, educational attainment, and race/ethnicity. However, multivariate analysis identified electronic gambling machine (EGM) participation to be the primary predictor of problem gambling status, with race/ethnicity, presence of a mood disorder, male gender, casino table game participation, older age, a greater level of smoking, participation in speculative financial activity, instant lottery participation, lower household income, and lottery or raffle ticket participation providing additional predictive power. Provincial EGM density and EGM participation rates are also very strong predictors of provincial rates of at-risk and problem gambling. CONCLUSION: Problem gambling has a biopsychosocial etiology, determined by personal vulnerability factors combined with the presence of riskier types of gambling such as EGMs. Effective prevention requires a multifaceted approach, but constraints on the availability and operation of EGMs would likely have the greatest single public health benefit.

RéSUMé: OBJECTIFS: Présenter un profil actualisé des joueurs et des joueurs pathologiques au Canada et cerner les caractéristiques les plus fortement associées au jeu pathologique. MéTHODE: Une évaluation de la participation au jeu de hasard et du jeu pathologique figurant dans l'Enquête sur la santé dans les collectivités canadiennes de 2018 a été administrée à 23 952 personnes de 18 ans et plus. Le profil démographique de chaque type de participation au jeu de hasard et la catégorie de joueur (non-joueur, joueur non pathologique, joueur à risque, joueur pathologique) ont été établis par statistique descriptive. Une régression logistique a permis de cerner les caractéristiques qui distinguaient le mieux les joueurs pathologiques des joueurs non pathologiques. RéSULTATS: La participation au jeu de hasard et le jeu pathologique variaient tous les deux en fonction du sexe, du revenu, du niveau d'instruction et de la race/l'ethnicité. L'analyse multivariée a cependant déterminé que l'utilisation d'appareils électroniques de jeu (AÉJ) était la principale variable prédictive du jeu pathologique, et que la race/l'ethnicité, la présence d'un trouble de l'humeur, le sexe masculin, la participation aux jeux de table dans les casinos, l'âge avancé, le tabagisme important, la participation à des activités financières spéculatives, la participation aux loteries instantanées, le faible revenu du ménage et l'achat de billets de loterie ou de tirage au sort amélioraient le pouvoir de prédiction. La densité provinciale des AÉJ et les taux d'utilisation des AÉJ étaient aussi de très fortes variables prédictives des taux provinciaux de jeu à risque et de jeu pathologique. CONCLUSION: Le jeu pathologique présente une étiologie biopsychosociale déterminée par des facteurs de vulnérabilité personnels combinés à la présence de types de jeu de hasard plus risqués, comme les AÉJ. Une prévention efficace nécessite une démarche pluridimensionnelle, mais l'imposition de limites à la disponibilité et à l'utilisation des AÉJ serait probablement la solution la plus avantageuse sur le plan de la santé publique.

Gambling and Problem Gambling in Canada in 2018: Prevalence and Changes Since 2002.

OBJECTIVE: The purpose of this study was to provide an updated profile of gambling and problem gambling in Canada and to examine how the rates and pattern of participation compare to 2002. METHOD: An assessment of gambling and problem gambling was included in the 2018 Canadian Community Health Survey and administered to 24,982 individuals aged 15 and older. The present analyses selected for adults (18+). RESULTS: A total of 66.2% of people reported engaging in some type of gambling in 2018, primarily lottery and/or raffle tickets, the only type in which the majority of Canadians participate. There are some significant interprovincial differences, with perhaps the most important one being the higher rate of electronic gambling machine (EGM) participation in Manitoba and Saskatchewan. The overall pattern of gambling in 2018 is very similar to 2002, although participation is generally much lower in 2018, particularly for EGMs and bingo. Only 0.6% of the population were identified as problem gamblers in 2018, with an additional 2.7% being at-risk gamblers. There is no significant interprovincial variation in problem gambling rates. The interprovincial pattern of problem gambling in 2018 is also very similar to what was found in 2002 with the main difference being a 45% decrease in the overall prevalence of problem gambling. CONCLUSIONS: Gambling and problem gambling have both decreased in Canada from 2002 to 2018 although the provincial patterns are quite similar between the 2 time periods. Several mechanisms have likely collectively contributed to these declines. Decreases have also been reported in several other Western countries in recent years and have occurred despite the expansion of legal gambling opportunities, suggesting a degree of inoculation or adaptation in large parts of the population.

EphA7 isoforms differentially regulate cortical dendrite development.

The shape of a neuron facilitates its functionality within neural circuits. Dendrites integrate incoming signals from axons, receiving excitatory input onto small protrusions called dendritic spines. Therefore, understanding dendritic growth and development is fundamental for discerning neural function. We previously demonstrated that EphA7 receptor signaling during cortical development impacts dendrites in two ways: EphA7 restricts dendritic growth early and promotes dendritic spine formation later. Here, the molecular basis for this shift in EphA7 function is defined. Expression analyses reveal that EphA7 full-length (EphA7-FL) and truncated (EphA7-T1; lacking kinase domain) isoforms are dynamically expressed in the developing cortex. Peak expression of EphA7-FL overlaps with dendritic elaboration around birth, while highest expression of EphA7-T1 coincides with dendritic spine formation in early postnatal life. Overexpression studies in cultured neurons demonstrate that EphA7-FL inhibits both dendritic growth and spine formation, while EphA7-T1 increases spine density. Furthermore, signaling downstream of EphA7 shifts during development, such that in vivo inhibition of mTOR by rapamycin in EphA7-mutant neurons ameliorates dendritic branching, but not dendritic spine phenotypes. Finally, direct interaction between EphA7-FL and EphA7-T1 is demonstrated in cultured cells, which results in reduction of EphA7-FL phosphorylation. In cortex, both isoforms are colocalized to synaptic fractions and both transcripts are expressed together within individual neurons, supporting a model where EphA7-T1 modulates EphA7-FL repulsive signaling during development. Thus, the divergent functions of EphA7 during cortical dendrite development are explained by the presence of two variants of the receptor.

The road best traveled: Neural crest migration upon the extracellular matrix.

Neural crest cells have the extraordinary task of building much of the vertebrate body plan, including the craniofacial cartilage and skeleton, melanocytes, portions of the heart, and the peripheral nervous system. To execute these developmental programs, stationary premigratory neural crest cells first acquire the capacity to migrate through an extensive process known as the epithelial-to-mesenchymal transition. Once motile, neural crest cells must traverse a complex environment consisting of other cells and the protein-rich extracellular matrix in order to get to their final destinations. Herein, we will highlight some of the main molecular machinery that allow neural crest cells to first exit the neuroepithelium and then later successfully navigate this intricate in vivo milieu. Collectively, these extracellular and intracellular factors mediate the appropriate migration of neural crest cells and allow for the proper development of the vertebrate embryo.

The relationship between gambling fallacies and problem gambling.

The cognitive model of problem gambling posits that erroneous gambling-related fallacies are key in the development and maintenance of problem gambling. However, this contention is based on cross-sectional rather than longitudinal associations between these constructs, and gambling fallacy instruments that may have inflated this associated by their inclusion of problem gambling symptomatology. The current research re-evaluates the relationship between problem gambling and gambling-specific erroneous cognitions in a 5-year longitudinal study of gambling using a psychometrically sound measure of erroneous gambling-related cognitions. The sample used in this study (n = 4,121) was recruited from the general population in Ontario, Canada, and the retention rate over 5 years was exceptionally high (93.9%). The total sample was similar, in age and gender distributions, to the census data at the time of data collection for Canadian adults (18-24 years, n = 265, 55.8% female; 25-44 years, n = 1,667, 56.4% female; 45-64 years, n = 1,731, 55.4% female; 65 + years, n = 458, 44.75% female). Results of both cross-sectional and longitudinal analyses confirm that gambling-specific fallacies appear to be etiologically related to the subsequent appearance of problem gambling, but to a weaker degree than previously presumed, and in a bidirectional manner. (PsycINFO Database Record

Development and Validation of the Poker Skills Measure (PSM).

Existing research has demonstrated that poker is a game predominated by skill. Little is known about the specific characteristics of good poker players however, likely due in part to the lack of a readily available measure of poker skill. In the absence of an available and easily administered poker skill measure, laboratory studies of poker player attributes have used questionable methodologies to assess skill including peer- and self-report. The aim of the current research was to create a valid, reliable, and easily administered measure of poker playing skill. A sample of 100 University of Lethbridge undergraduate students and Lethbridge community members completed the newly created Poker Skills Measure (PSM) and an objective measure of poker playing performance (playing virtual poker). External validity of the measure was demonstrated via significant associations­expected and detected­between the PSM and the objective playing measure. Specifically, significant positive associations were found between PSM scores and hands won, pre- and post flop aggression, and a significant negative relationship was detected between PSM scores and number of hands played. Within the current sample, acceptable internal consistency (Cronbach's α = .82) and very good test re-test reliability (r = .78) was achieved with the 35 item PSM. Future directions are discussed.

From student to steward: the Interdisciplinary Program in Neuroscience at Georgetown University as a case study in professional development during doctoral training.

A key facet of professional development is the formation of professional identity. At its most basic level, professional identity for a scientist centers on mastery of a discipline and the development of research skills during doctoral training. To develop a broader understanding of professional identity in the context of doctoral training, the Carnegie Initiative on the Doctorate (CID) ran a multi-institutional study from 2001 to 2005. A key outcome of the CID was the development of the concept of 'stewards of the discipline'. The Interdisciplinary Program in Neuroscience (IPN) at Georgetown University participated in CID from 2003 to 2005. Here, we describe the IPN and highlight the programmatic developments resulting from participation in the CID. In particular, we emphasize programmatic activities that are designed to promote professional skills in parallel with scientific development. We describe activities in the domains of leadership, communication, teaching, public outreach, ethics, collaboration, and mentorship. Finally, we provide data that demonstrate that traditional metrics of academic success are not adversely affected by the inclusion of professional development activities in the curricula. By incorporating these seven 'professional development' activities into the required coursework and dissertation research experience, the IPN motivates students to become stewards of the discipline.

EphA7 signaling guides cortical dendritic development and spine maturation.

The process by which excitatory neurons are generated and mature during the development of the cerebral cortex occurs in a stereotyped manner; coordinated neuronal birth, migration, and differentiation during embryonic and early postnatal life are prerequisites for selective synaptic connections that mediate meaningful neurotransmission in maturity. Normal cortical function depends upon the proper elaboration of neurons, including the initial extension of cellular processes that lead to the formation of axons and dendrites and the subsequent maturation of synapses. Here, we examine the role of cell-based signaling via the receptor tyrosine kinase EphA7 in guiding the extension and maturation of cortical dendrites. EphA7, localized to dendritic shafts and spines of pyramidal cells, is uniquely expressed during cortical neuronal development. On patterned substrates, EphA7 signaling restricts dendritic extent, with Src and Tsc1 serving as downstream mediators. Perturbation of EphA7 signaling in vitro and in vivo alters dendritic elaboration: Dendrites are longer and more complex when EphA7 is absent and are shorter and simpler when EphA7 is ectopically expressed. Later in neuronal maturation, EphA7 influences protrusions from dendritic shafts and the assembling of synaptic components. Indeed, synaptic function relies on EphA7; the electrophysiological maturation of pyramidal neurons is delayed in cultures lacking EphA7, indicating that EphA7 enhances synaptic function. These results provide evidence of roles for Eph signaling, first in limiting the elaboration of cortical neuronal dendrites and then in coordinating the maturation and function of synapses.

Parcellation of the thalamus into distinct nuclei reflects EphA expression and function.

Intercellular signaling via the Eph receptor tyrosine kinases and their ligands, the ephrins, acts to shape many regions of the developing brain. One intriguing consequence of Eph signaling is the control of mixing between discrete cell populations in the developing hindbrain, contributing to the formation of segregated rhombomeres. Since the thalamus is also a parcellated structure comprised of discrete nuclei, might Eph signaling play a parallel role in cell segregation in this brain structure? Analyses of expression reveal that several Eph family members are expressed in the forming thalamus and that cells expressing particular receptors form cellular groupings as development proceeds. Specifically, expression of receptors EphA4 or EphA7 and ligand ephrin-A5 is localized to distinct thalamic domains. EphA4 and EphA7 are often coexpressed in regions of the forming thalamus, with each receptor marking discrete thalamic domains. In contrast, ephrin-A5 is expressed by a limited group of thalamic cells. Within the ventral thalamus, EphA4 is present broadly, occasionally overlapping with ephrin-A5 expression. EphA7 is more restricted in its expression and is largely nonoverlapping with ephrin-A5. In mutant mice lacking one or both receptors or ephrin-A5, the appearance of the venteroposterolateral (VPL) and venteroposteromedial (VPM) nuclear complex is altered compared to wild type mice. These in vivo results support a role for Eph family members in the definition of the thalamic nuclei. In parallel, in vitro analysis reveals a hierarchy of mixing among cells expressing ephrin-A5 with cells expressing EphA4 alone, EphA4 and EphA7 together, or EphA7 alone. Together, these data support a model in which EphA molecules promote the parcellation of discrete thalamic nuclei by limiting the extent of cell mixing.

Prospective memory, personality, and individual differences.

A number of studies investigating the relationship between personality and prospective memory (ProM) have appeared during the last decade. However, a review of these studies reveals little consistency in their findings and conclusions. To clarify the relationship between ProM and personality, we conducted two studies: a meta-analysis of prior research investigating the relationships between ProM and personality, and a study with 378 participants examining the relationships between ProM, personality, verbal intelligence, and retrospective memory. Our review of prior research revealed great variability in the measures used to assess ProM, and in the methodological quality of prior research; these two factors may partially explain inconsistent findings in the literature. Overall, the meta-analysis revealed very weak correlations (rs ranging from 0.09 to 0.10) between ProM and three of the Big Five factors: Openness, Conscientiousness, and Agreeableness. Our experimental study showed that ProM performance was related to individual differences such as verbal intelligence as well as to personality factors and that the relationship between ProM and personality factors depends on the ProM subdomain. In combination, the two studies suggest that ProM performance is relatively weakly related to personality factors and more strongly related to individual differences in cognitive factors.

Mesoscale eddies drive increased silica export in the subtropical Pacific Ocean.

Mesoscale eddies may play a critical role in ocean biogeochemistry by increasing nutrient supply, primary production, and efficiency of the biological pump, that is, the ratio of carbon export to primary production in otherwise nutrient-deficient waters. We examined a diatom bloom within a cold-core cyclonic eddy off Hawaii. Eddy primary production, community biomass, and size composition were markedly enhanced but had little effect on the carbon export ratio. Instead, the system functioned as a selective silica pump. Strong trophic coupling and inefficient organic export may be general characteristics of community perturbation responses in the warm waters of the Pacific Ocean.