Long-term potentiation: 50 years on: past, present and future.

We introduce and summarize reviews and research papers by speakers at a discussion meeting on 'Long-term potentiation: 50 years on' held at the Royal Society, London, on 20-21 November 2023. The meeting followed earlier discussion meetings marking the 30th and 40th anniversaries of the discovery of long-term potentiation. These new contributions give an overview of current research and controversies in a vibrant branch of neuroscience with important implications for our understanding of the neurobiological basis of many forms of learning and memory and a wide spectrum of neurological and cognitive disorders.This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

An invertebrate model in examining the effect of acute ferric iron exposure on proprioceptive neurons.

Iron is an essential element for plant and animal life and is found in soil, fresh waters and marine waters. The Fe3+ ion is a vital prosthetic group and cofactor to mitochondrial electron transport complexes and numerous proteins involved in normal functioning. Despite its importance to life-sustaining processes, overexposure results in toxicity. For example, ferric iron (Fe3+) accumulation in the mammalian central nervous system is associated with various neurological disorders. Although current literature addresses the long-term effects of Fe3+ overload, fewer studies exist examining the effects of acute exposure. Using the blue crab (Callinectes sapidus), we investigate the effects of acute Fe3+ overload on proprioception within the propodite-dactylopodite (PD) nerve. For proprioceptive studies, 10- and 20-mM ferric chloride and ferric ammonium citrate solutions were used at 5- and 20- min exposure times. Exposure to 20 mM concentrations of ferric chloride and ferric ammonium citrate reduced excitability in proprioceptive neurons. Thus, Fe3+ likely blocks stretch-activated channels or voltage-gated Na+ channels. The depressive effects of Fe3+ are partly reversible following saline washout, indicating cells are not acutely damaged. Gadolinium (GdCl3, 1 and 10 mM) was used to examine the effects of an additional trivalent ion comparator. Gd3+ depressed PD nerve compound action potential amplitude while increasing the compound action potential duration. This study is relevant in demonstrating the dose-dependent effects of acute Fe3+ and Gd3+ exposure on proprioception and provides a model system to further investigate the mechanisms by which metals act on the nervous system.

Estimating Joint Health State Utility Algorithms Under Partial Information.

OBJECTIVES: We explored the performance of existing joint health state utility estimators when data are not available on utilities that isolate single-condition health states excluding any co-occurring condition. METHODS: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions-III, we defined 2 information sets: (1) a full-information set that includes the narrowly defined health state utilities used in most studies that test the performance of joint health state utility estimators, and (2) a limited information set that includes only the more broadly defined health state utilities more commonly available to researchers. We used an example of alcohol use disorder co-occurring with cirrhosis of the liver, depressive disorder, or nicotine use disorder to illustrate our analysis. RESULTS: We found that the performance of joint health state utility estimators is appreciably different under limited information than under full information. Full-information estimators typically overestimate the joint state utility, whereas limited-information estimators underestimate the joint state utility, except for the minimum estimator, which is overestimated in all cases. CONCLUSIONS: Researchers using joint health state utility estimators should understand the information set available to them and use methodological guidance appropriate for that information set. We recommend the minimum estimator under limited information based on its ease of use, consistency (and therefore a predictable direction of bias), and lower root mean squared error.

A Practical Guide to Genetic Testing for Kidney Disorders of Unknown Etiology.

Genetic testing is increasingly used in the workup and diagnosis of kidney disease and kidney-related disorders of undetermined cause. Out-of-pocket costs for clinical genetic testing have become affordable, and logistical hurdles overcome. The interest in genetic testing may stem from the need to make or confirm a diagnosis, guide management, or the patient's desire to have a more informed explanation or prognosis. This poses a challenge for providers who do not have formal training in the selection, interpretation, and limitations of genetic tests. In this manuscript, we provide detailed discussion of relevant cases in which clinical genetic testing using a kidney gene panel was applied. The cases demonstrate identification of pathogenic variants for monogenic diseases-contrasting them from genetic risk alleles-and bring up diagnostic limitations and diagnostic utility of these tests in nephrology. This review aims to guide clinicians in formulating pretest conversations with their patients, interpreting genetic variant nomenclature, and considering follow-up investigations. Although providers are gaining experience, there is still risk of testing causing more anxiety than benefit. However, with provider education and support, clinical genetic testing applied to otherwise unexplained kidney-related disorders will increasingly serve as a valuable diagnostic tool with the potential to reshape how we consider and treat many kidney-related diagnoses.

COVID-19 reinfection in Liberia: Implication for improving disease surveillance.

COVID-19 remains a serious disruption to human health, social, and economic existence. Reinfection with the virus intensifies fears and raises more questions among countries, with few documented reports. This study investigated cases of COVID-19 reinfection using patients' laboratory test results between March 2020 and July 2021 in Liberia. Data obtained from Liberia's Ministry of Health COVID-19 surveillance was analyzed in Excel 365 and ArcGIS Pro 2.8.2. Results showed that with a median interval of 200 days (Range: 99-415), 13 out of 5,459 cases were identified and characterized as reinfection in three counties during the country's third wave of the outbreak. Eighty-six percent of the COVID-19 reinfection cases occurred in Montserrado County within high clusters, which accounted for over 80% of the randomly distributed cases in Liberia. More cases of reinfection occurred among international travelers within populations with high community transmissions. This study suggests the need for continued public education and surveillance to encourage longer-term COVID-19 preventive practices even after recovery.

Glutamate receptors and synaptic plasticity: The impact of Evans and Watkins.

On the occasion of the 40 year anniversary of the hugely impactful review by Richard (Dick) Evans and Jeff Watkins, we describe how their work has impacted the field of synaptic plasticity. We describe their influence in each of the major glutamate receptor subtypes: AMPARs, NMDARs, KARs and mGluRs. Particular emphasis is placed on how their work impacted our own studies in the hippocampus. For example, we describe how the tools and regulators that they identified for studying NMDARs (e.g., NMDA, D-AP5 and Mg2+) led to the understanding of the molecular basis of the induction of LTP. We also describe how other tools that they introduced (e.g., (1S,3R)-ACPD and MCPG) helped lead to the concept of metaplasticity.

Measurement invariance of suicide screening measures across military branch.

Military suicide rates are near all-time highs. To help clinicians and researchers study suicide risk factors in military samples, the Military Suicide Research Consortium (MSRC) developed a set of brief suicide-risk screening measures. While previous research has examined the reliability of these screening measures, it remains unclear if measurement differences exist across different military branches. This is an important omission given that establishing measurement equivalence or invariance (ME/I) across groups is a prerequisite for making group comparisons, which are necessary for accurately identifying and effectively intervening with groups at heightened risk. This study examined the ME/I of four MSRC screening measures (e.g., Depressive Symptom Index - Suicidality Subscale; Interpersonal Needs Questionnaire; Suicidal Behaviors Questionnaire - Revised; Suicide Intent Scale) using a sample of 4,487 participants across military branches (Army; National Guard; Navy; Marine; Air Force) using a series of multiple-group confirmatory factor analyses (MGCFA). We assessed configural, threshold, and loading invariance, with results indicating that the brief screening measures are fully invariant between individuals from different military branches and that these suicide screeners can be used to examine differences across branches in future research. Research and applied implications are discussed.

A Cultural Comparison of Personality Profiles of U.S. and Japanese Centenarians.

The purpose of this study was a cross-cultural examination of centenarians' personality through a person-centered approach to examine if there is a "resilient" personality profile consistent across cultures. Proxy reports information was obtained from family and close friends of 239 U.S. centenarians from the Georgia Centenarians Study and 272 Japanese centenarians from the Tokyo Centenarian Study. Latent profile analyses were conducted to identify personality profiles in centenarians from the United States and Japan. Two personality profiles were identified in both samples: a "resilient" personality profile and "nonresilient" personality profile. The "resilient" group had higher levels of positive personality traits with higher scores on agreeableness and extraversion and lower scores on neuroticism, conscientiousness, and openness. The "nonresilient" group had higher scores on neuroticism and lower scores on extraversion, openness, agreeableness, and conscientiousness. Fifty percent of U.S. centenarians and 65% of Japanese centenarians were in the "resilient" group.

Modeling cohesion change in group counseling: The role of client characteristics, group variables, and leader behaviors.

Despite continued empirical support for a relationship between group cohesion and therapeutic gain, few studies have attempted to examine predictors of cohesion during the life of counseling groups. The present investigation explored the impact of client variables, group characteristics, and first-session leader behaviors on changes in cohesion across time. Participants were 128 volunteer clients and 14 group therapists participating in 23 separate 8-week-long counseling groups. Results of latent growth curve (LGC) analysis indicated that a piecewise, linear-quadratic model best fit the data at the individual level, while a simplified linear model best fit the data at the group level. Overall, individual differences accounted for 80-97% of the total variance in cohesion intercept and slope terms, with the included covariates explaining 9-39% of this variation. Significant individual-level covariates were gender and anxious and avoidant attachment. The only significant group-level predictor was an interaction effect between leadership behaviors in the first session. Specifically, when leaders performed a high number of structuring behaviors in the absence of facilitating emotional sharing, cohesion was lower at the end of the first session. Limitations, areas of future research, and implications for the theory and practice of brief group counseling are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Environmental enrichment effects on synaptic and cellular physiology of hippocampal neurons.

Exposure of rodents to an enriched environment (EE) has been shown to reliably increase performance on hippocampus-dependent learning and memory tasks, compared to conspecifics living in standard housing conditions. Here we review the EE-related functional changes in synaptic and cellular properties for neurons in the dentate gyrus and area CA1, as assessed through in vivo and ex vivo electrophysiological approaches. There is a growing consensus of findings regarding the pattern of effects seen. Most prominently, there are changes in cellular excitability and synaptic plasticity in CA1, particularly with short-term and/or periodic exposure to EE. Such changes are much less evident after longer term continuous exposure to EE. In the dentate gyrus, increases in synaptic transmission as well as cell excitability become evident after short-term EE exposure, while the induction of long-term potentiation (LTP) in the dentate is remarkably insensitive, even though it is reliably enhanced by voluntary running. Recent evidence has added a new dimension to the understanding of EE effects on hippocampal electrophysiology by revealing an increased sparsity of place cell representations after long periods of EE treatment. It is possible that such connectivity change is one of the key factors contributing to the enhancement of hippocampus-dependent spatial learning over the long-term, even if there are no obvious changes in other markers such as LTP. This article is part of the Special Issue entitled "Neurobiology of Environmental Enrichment".

Family health and income: A two-sample replication.

The current study examined psychological and family health predictors of change over time in household income, using data from longitudinal studies of African American (N = 889, 93.5% female) and Mexican origin (N = 674, 100% female) families. Participants self-reported their household income, as well as their emotional, personality, and cognitive resources. Participant behavioral and physical resources were coded from observed family interactions. Although income did not predict change in any personal resources, all five classes of personal resources (i.e., emotional, personality, cognitive, behavioral, physical) predicted change in income across a 10-year span (Study 1) and a 6-year span (Study 2). Income is potentially caused by these personal resources, or both income and these personal resources share a common cause. The dominant approach of assuming income causes personal and family health needs stronger support. (PsycINFO Database Record

Altered plasma arginine metabolome precedes behavioural and brain arginine metabolomic profile changes in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease.

While amyloid-beta (Aß) peptides play a central role in the development of Alzheimer's disease (AD), recent evidence also implicates altered metabolism of L-arginine in the pathogenesis of AD. The present study systematically investigated how behavioural function and the brain and plasma arginine metabolic profiles changed in a chronic Aß accumulation model using male APPswe/PS1ΔE9 transgenic (Tg) mice at 7 and 13 months of age. As compared to their wild-type (WT) littermates, Tg mice displayed age-related deficits in spatial water maze tasks and alterations in brain arginine metabolism. Interestingly, the plasma arginine metabolic profile was markedly altered in 7-month Tg mice prior to major behavioural impairment. Receiver operating characteristic curve analysis revealed that plasma putrescine and spermine significantly differentiated between Tg and WT mice. These results demonstrate the parallel development of altered brain arginine metabolism and behavioural deficits in Tg mice. The altered plasma arginine metabolic profile that preceded the behavioural and brain profile changes suggests that there may be merit in an arginine-centric set of ante-mortem biomarkers for AD.

Adult-born dentate granule cell excitability depends on the interaction of neuron age, ontogenetic age and experience.

Early during their maturation, adult-born dentate granule cells (aDGCs) are particularly excitable, but eventually develop the electrophysiologically quiet properties of mature cells. However, the stability versus plasticity of this quiet state across time and experience remains unresolved. By birthdating two populations of aDGCs across different animal ages, we found for 10-month-old rats the expected reduction in excitability across cells aged 4-12 weeks, as determined by Egr1 immunoreactivity. Unexpectedly, cells 35 weeks old (after genesis at an animal age of 2 months) were as excitable as 4-week-old cells, in the dorsal hippocampus. This high level of excitability at maturity was specific for cells born in animals 2 months of age, as cells born later in life did not show this effect. Importantly, excitability states were not fixed once maturity was gained, but were enhanced by enriched environment exposure or LTP induction, indicating that any maturational decrease in excitability can be compensated by experience. These data reveal the importance of the animal's age for aDGC excitability, and emphasize their prolonged capability for plasticity during adulthood.

Neighborhood racial discrimination and the development of major depression.

This study examined the impact of neighborhood racial discrimination on the development of major depressive disorder (MDD) in a sample of African American women. Participants were 499 women from Georgia and Iowa with no history of MDD who were followed for 9 to 11 years. Several neighborhood characteristics (community social disorder, community cohesion, and community racism) and individual characteristics (negative life events, financial strain, personal outlook, religious involvement, relationship quality, negative affectivity, and individual experiences of racism) were employed as predictors of whether or not the women met criteria for MDD during this period of time. In a multilevel logistic regression analysis, neighborhood-level discrimination as well as individual-level variables including the number of negative life events, financial strain, and negative affectivity were found to be significant predictors of developing MDD. Analyses of cross-level interactions indicated that the effects of neighborhood-level discrimination were moderated by the quality of individuals' relationships, such that better relationships with others served to lessen the effect of neighborhood discrimination on depression. Implications of these findings for understanding the negative effects of racial discrimination are discussed. (PsycINFO Database Record