Genes Brain and Behavior最新文献

{"title":"Rapid auditory processing and medial geniculate nucleus anomalies in Kiaa0319 knockout mice","authors":"Peter A. Perrino,&nbsp;Renee Y. Chasse,&nbsp;Anthony P. Monaco,&nbsp;Zoltán Molnár,&nbsp;Antonio Velayos-Baeza,&nbsp;R. Holly Fitch","doi":"10.1111/gbb.12808","DOIUrl":"10.1111/gbb.12808","url":null,"abstract":"<p>Developmental dyslexia is a common neurodevelopmental disorder characterized by difficulties in reading and writing. Although underlying biological and genetic mechanisms remain unclear, anomalies in phonological processing and auditory processing have been associated with dyslexia. Several candidate risk genes have also been identified, with <i>KIAA0319</i> as a main candidate. Animal models targeting the rodent homolog (<i>Kiaa0319</i>) have been used to explore putative behavioral and anatomic anomalies, with mixed results. For example after downregulation of <i>Kiaa0319</i> expression in rats via shRNA, significant adult rapid auditory processing impairments were reported, along with cortical anomalies reflecting atypical neuronal migration. Conversely, <i>Kiaa0319</i> knockout (KO) mice were reported to have typical adult auditory processing, and no visible cortical anomalies. To address these inconsistencies, we tested <i>Kiaa0319</i> KO mice on auditory processing tasks similar to those used previously in rat shRNA knockdown studies. Subsequent neuroanatomic analyses on these same mice targeted medial geniculate nucleus (MGN), a receptive communication-related brain structure. Results confirm that <i>Kiaa0319</i> KO mice exhibit significant auditory processing impairments specific to rapid/brief stimuli, and also show significant volumetric reductions and a shift toward fewer large and smaller neurons in the MGN. The latter finding is consistent with post mortem MGN data from human dyslexic brains. Combined evidence supports a role for <i>KIAA0319</i> in the development of auditory CNS pathways subserving rapid auditory processing functions critical to the development of speech processing, language, and ultimately reading. Results affirm <i>KIAA0319</i> variation as a possible risk factor for dyslexia specifically via anomalies in central acoustic processing pathways.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/47/9a/GBB-21-e12808.PMC9744489.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10668101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological functions of α2-adrenergic-like octopamine receptor in Drosophila melanogaster","authors":"Hiroyuki Nakagawa,&nbsp;Shiori Maehara,&nbsp;Kazuhiko Kume,&nbsp;Hiroto Ohta,&nbsp;Jun Tomita","doi":"10.1111/gbb.12807","DOIUrl":"10.1111/gbb.12807","url":null,"abstract":"<p>Octopamine regulates various physiological phenomena including memory, sleep, grooming and aggression in insects. In <i>Drosophila</i>, four types of octopamine receptors have been identified: <i>Oamb</i>, <i>Oct/TyrR</i>, <i>OctβR</i> and <i>Octα2R</i>. Among these receptors, <i>Octα2R</i> was recently discovered and pharmacologically characterized. However, the effects of the receptor on biological functions are still unknown. Here, we showed that <i>Octα2R</i> regulated several behaviors related to octopamine signaling. <i>Octα2R</i> hypomorphic mutant flies showed a significant decrease in locomotor activity. We found that <i>Octα2R</i> expressed in the pars intercerebralis, which is a brain region projected by octopaminergic neurons, is involved in control of the locomotor activity. Besides, <i>Octα2R</i> hypomorphic mutants increased time and frequency of grooming and inhibited starvation-induced hyperactivity. These results indicated that <i>Octα2R</i> expressed in the central nervous system is responsible for the involvement in physiological functions.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7b/34/GBB-21-e12807.PMC9744561.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10668094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in GABAA receptor subunit transcript expression are mediated by genotype in subjects with alcohol-related cirrhosis of the liver","authors":"Madeline K. Ashton,&nbsp;André V. L. Rueda,&nbsp;Ada M.-C. Ho,&nbsp;Noradibah Arina Binte M. Noor Aizin,&nbsp;Hansa Sharma,&nbsp;Peter R. Dodd,&nbsp;Alfreda Stadlin,&nbsp;Rosana Camarini","doi":"10.1111/gbb.12785","DOIUrl":"https://doi.org/10.1111/gbb.12785","url":null,"abstract":"<p>Male and female human subjects show contrasting propensities to misuse drugs of addiction, including alcohol. These differences lead to different psychological and neurological consequences, such as the likelihood of developing dependence. The pattern and extent of brain damage in alcohol-use disorder cases also varies with comorbid disease. To explore mechanisms that might underlie these outcomes, we used autopsy tissue to determine mRNA transcript expression in relation to genotype for two GABA_A receptor subunit genes. We used quantitative Real-Time PCR to measure <i>GABRA6</i> and <i>GABRA2</i> mRNA concentrations in dorsolateral prefrontal and primary motor cortices of alcohol-use disorder subjects and controls of both sexes with and without liver disease who had been genotyped for these GABA_A receptor subunit genes. Cirrhotic alcohol-use disorder cases had significantly higher expression of <i>GABRA6</i> and <i>GABRA2</i> transcripts than either controls or non-cirrhotic alcohol-use disorder cases. Differences were observed between sexes, genotypes and brain regions. We show that sex differences in subjects with <i>GABRA6</i> and <i>GABRA2</i> variants may contribute to differences in susceptibility to alcohol-use disorder and alcohol-induced cirrhosis.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12785","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71965215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PACAP-expressing neurons in the lateral habenula diminish negative emotional valence","authors":"Marjorie R. Levinstein,&nbsp;David J. Bergkamp,&nbsp;Zoë K. Lewis,&nbsp;Alex Tsobanoudis,&nbsp;Koichi Hashikawa,&nbsp;Garret D. Stuber,&nbsp;John F. Neumaier","doi":"10.1111/gbb.12801","DOIUrl":"10.1111/gbb.12801","url":null,"abstract":"<p>The lateral habenula (LHb) is a small, bilateral, epithalamic nucleus which processes aversive information. While primarily glutamatergic, LHb neurons express genes coding for many neuropeptides, such as <i>Adcyap1</i> the gene encoding pituitary adenylate cyclase-activating polypeptide (PACAP), which itself has been associated with anxiety and stress disorders. Using Cre-dependent viral vectors, we targeted and characterized these neurons based on their anatomical projections and found that they projected to both the raphe and rostromedial tegmentum but only weakly to ventral tegmental area. Using RiboTag to capture ribosomal-associated mRNA from these neurons and reanalysis of existing single cell RNA sequencing data, we did not identify a unique molecular phenotype that characterized these PACAP-expressing neurons in LHb. In order to understand the function of these neurons, we conditionally expressed hM₃Dq DREADD selectively in LHb PACAP-expressing neurons and chemogenetically excited these neurons during behavioral testing in the open field test, contextual fear conditioning, sucrose preference, novelty suppressed feeding, and conditioned place preference. We found that Gq activation of these neurons produce behaviors opposite to what is expected from the LHb as a whole—they decreased anxiety-like and fear behavior and produced a conditioned place preference. In conclusion, PACAP-expressing neurons in LHb represents a molecularly diverse population of cells that oppose the actions of the remainder of LHb neurons by being rewarding or diminishing the negative consequences of aversive events.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c9/8c/GBB-21-e12801.PMC9444940.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9333130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and environmental influences on quality of life: The COVID-19 pandemic as a natural experiment","authors":"Margot P. van de Weijer,&nbsp;Dirk H. M. Pelt,&nbsp;Lianne P. de Vries,&nbsp;Floris Huider,&nbsp;Matthijs D. van der Zee,&nbsp;Quinta Helmer,&nbsp;Lannie Ligthart,&nbsp;Gonneke Willemsen,&nbsp;Dorret I. Boomsma,&nbsp;Eco de Geus,&nbsp;Meike Bartels","doi":"10.1111/gbb.12796","DOIUrl":"10.1111/gbb.12796","url":null,"abstract":"<p>By treating the coronavirus disease 2019 (COVID-19) pandemic as a natural experiment, we examine the influence of substantial environmental change (i.e., lockdown measures) on individual differences in quality of life (QoL) in the Netherlands. We compare QoL scores before the pandemic (<i>N</i> = 25,772) to QoL scores during the pandemic (<i>N</i> = 17,222) in a sample of twins and their family members. On a 10-point scale, we find a significant decrease in mean QoL from 7.73 (SD = 1.06) before the pandemic to 7.02 (SD = 1.36) during the pandemic (Cohen's <i>d</i> = 0.49). Additionally, variance decomposition shows an increase in unique environmental variance during the pandemic (0.30–1.08), and a decrease in the heritability estimate from 30.9% to 15.5%. We hypothesize that the increased environmental variance is the result of lockdown measures not impacting everybody equally. Whether these effects persist over longer periods and how they impact health inequalities remain topics for future investigation.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9111595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10347196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconsidering animal models used to study autism spectrum disorder: Current state and optimizing future","authors":"Jill L. Silverman,&nbsp;Audrey Thurm,&nbsp;Sarah B. Ethridge,&nbsp;Makayla M. Soller,&nbsp;Stela P. Petkova,&nbsp;Ted Abel,&nbsp;Melissa D. Bauman,&nbsp;Edward S. Brodkin,&nbsp;Hala Harony-Nicolas,&nbsp;Markus Wöhr,&nbsp;Alycia Halladay","doi":"10.1111/gbb.12803","DOIUrl":"10.1111/gbb.12803","url":null,"abstract":"<p>Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and intellectual disability (ID), are pervasive, often lifelong disorders, lacking evidence-based interventions for core symptoms. With no established biological markers, diagnoses are defined by behavioral criteria. Thus, preclinical <i>in vivo</i> animal models of NDDs must be optimally utilized. For this reason, experts in the field of behavioral neuroscience convened a workshop with the goals of reviewing current behavioral studies, reports, and assessments in rodent models. Goals included: (a) identifying the maximal utility and limitations of behavior in animal models with construct validity; (b) providing recommendations for phenotyping animal models; and (c) guidelines on how <i>in vivo</i> models should be used and reported reliably and rigorously while acknowledging their limitations. We concluded by recommending minimal criteria for reporting in manuscripts going forward. The workshop elucidated a consensus of potential solutions to several problems, including revisiting claims made about animal model links to ASD (and related conditions). Specific conclusions included: mice (or other rodent or preclinical models) are models of the neurodevelopmental insult, not specifically any disorder (e.g., ASD); a model that perfectly recapitulates a disorder such as ASD is untenable; and greater attention needs be given to validation of behavioral testing methods, data analysis, and critical interpretation.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/71/f4/GBB-21-e12803.PMC9189007.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10670710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Under warm ambient conditions, Drosophila melanogaster suppresses nighttime activity via the neuropeptide pigment dispersing factor","authors":"Aishwariya Srikala Iyengar,&nbsp;Rutvij Kulkarni,&nbsp;Vasu Sheeba","doi":"10.1111/gbb.12802","DOIUrl":"10.1111/gbb.12802","url":null,"abstract":"<p>Rhythmic locomotor behaviour of flies is controlled by an endogenous time-keeping mechanism, the circadian clock, and is influenced by environmental temperatures. Flies inherently prefer cool temperatures around 25°C, and under such conditions, time their locomotor activity to occur at dawn and dusk. Under relatively warmer conditions such as 30°C, flies shift their activity into the night, advancing their morning activity bout into the early morning, before lights-ON, and delaying their evening activity into early night. The molecular basis for such temperature-dependent behavioural modulation has been associated with core circadian clock genes, but the neuronal basis is not yet clear. Under relatively cool temperatures such as 25°C, the role of the circadian pacemaker ventrolateral neurons (LNvs), along with a major neuropeptide secreted by them, pigment dispersing factor (PDF), has been showed in regulating various aspects of locomotor activity rhythms. However, the role of the LNvs and PDF in warm temperature-mediated behavioural modulation has not been explored. We show here that flies lacking proper PDF signalling or the LNvs altogether, cannot suppress their locomotor activity resulting in loss of sleep during the middle of the night, and thus describe a novel role for PDF signalling and the LNvs in behavioural modulation under warm ambient conditions. In a rapidly warming world, such behavioural plasticity may enable organisms to respond to harsh temperatures in the environment.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/80/ac/GBB-21-e12802.PMC9744560.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10670705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deepening the understanding of social bonding and dynamics of social interactions","authors":"Andrey E. Ryabinin","doi":"10.1111/gbb.12804","DOIUrl":"10.1111/gbb.12804","url":null,"abstract":"<p>The current volume continues the series of Genes, Brain and Behavior special issues. In the first special issue, we focused on autism and neurodevelopmental disorders.<span>¹</span> We concluded the issue with the idea that detailed understanding of these disorders is impossible without profound appreciation of mechanisms underlying natural species-specific social behaviors. Therefore, the current special issue directs readers' attention to fundamentals of social bonding, interactions, group/colony formation and even potential biology of human sociocultural experiences.</p><p>We start with social bonding, or social attachment. This topic has been not only an extensive subject of poetry and fictional literature, but has also been examined across multiple scientific disciplines, including psychology, anthropology, ethology, animal behavior, and cognitive neuroscience. Each of the disciplines provided explanations of this phenomenon in their own terms. A synthesis of these terms would be a substantial intellectual achievement. This need for synthesis is the cornerstone of the review by Gustison and Phelps,<span>²</span> the first article in this issue. The authors explore views on social attachment across multiple disciplines and then focus on pair-bond formation in prairie voles as a case study. The prairie vole (<i>Microtus ochrogaster)</i> is a socially monogamous rodent species. Studies of these species provided much insight into mechanisms of social bonding.<span>^{3, 4}</span> The authors describe the intricate molecular and circuitry mechanisms involved in individual differences in social bonding in prairie voles and provide an example of integration of this knowledge into multi-disciplinary language.</p><p>The next article, a review by Prior et al.<span>⁵</span> provides another type of integration of our understanding of mechanisms involved in social bonding. Specifically, the authors examine how much the social aspects of bond formation are dependent on the involved sensory and perceptual systems. They use the prairie vole and the zebra finch as examples of species, in which neurocircuitry of either chemical or vocal communication, and of social bonding, have been examined. The authors discuss the inter-dependence and bidirectional influences between specific sensory processes and social bonding. This exploration is followed by a framework for future studies in this field.</p><p>The reviews mentioned above are followed by two companion research papers, which challenge the simplified views on processes involved in pair bonding of prairie voles. They provide critical evidence against the idea of potential monomorphism in pair-bonding behaviors in these socially monogamous species. The article by Brusman et al.<span>⁶</span> compares indices of pair-bonding in the standard “choice” partner preference test<span>^{7, 8}</span> and a novel modified non-choice test across two time poi","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9744472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9239791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mutant allele of glycoprotein M6-B (Gpm6b) facilitates behavioral flexibility but increases delay discounting","authors":"Sandra Sanchez-Roige,&nbsp;Samuel A. Barnes,&nbsp;Jazlene Mallari,&nbsp;Rebecca Wood,&nbsp;Oksana Polesskaya,&nbsp;Abraham A. Palmer","doi":"10.1111/gbb.12800","DOIUrl":"10.1111/gbb.12800","url":null,"abstract":"<p>The neuronal membrane glycoprotein M6B (<i>Gpm6b</i>) gene encodes a membrane glycoprotein that belongs to the proteolipid protein family, and is enriched in neurons, oligodendrocytes, and subset of astrocytes in the central nervous system. GPM6B is thought to play a role in neuronal differentiation, myelination, and inactivation of the serotonin transporter via internalization. Recent human genome-wide association studies (GWAS) have implicated membrane glycoproteins (both <i>GPM6B</i> and <i>GPM6A</i>) in the regulation of traits relevant to psychiatric disorders, including neuroticism, depressed affect, and delay discounting. Mouse studies have implicated <i>Gpm6b</i> in sensorimotor gating and regulation of serotonergic signaling. We used CRISPR to create a mutant Glycoprotein M6B (<i>Gpm6b</i>) allele on a C57BL/6J mouse background. Because <i>Gpm6b</i> is located on the X chromosome, we focused on male <i>Gpm6b</i> mutant mice and their wild-type littermates (WT) in two behavioral tests that measured aspects of impulsive or flexible decision-making. We found that <i>Gpm6b</i> deletion caused deficits in a delay discounting task. In contrast, reward sensitivity was enhanced thereby facilitating behavioral flexibility and improving performance in the probabilistic reversal learning task. Taken together these data further delineate the role of <i>Gpm6b</i> in decision making behaviors that are relevant to multiple psychiatric disorders.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/91/e1/GBB-21-e12800.PMC9211103.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10662420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visuo-spatial learning and memory impairments in the 5xFAD mouse model of Alzheimer's disease: Effects of age, sex, albinism, and motor impairments","authors":"Timothy P. O'Leary,&nbsp;Richard E. Brown","doi":"10.1111/gbb.12794","DOIUrl":"10.1111/gbb.12794","url":null,"abstract":"<p>The 5xFAD mouse model of Alzheimer's disease (AD) rapidly develops AD-related neuro-behavioral pathology. Learning and memory impairments in 5xFAD mice, however, are not always replicated and the size of impairments varies considerably across studies. To examine possible sources of this variability, we analyzed the effects of age, sex, albinism due to background genes (<i>Tyr</i>^<i>c</i>, <i>Oca2</i>^<i>p</i>) and motor impairment on learning and memory performance of wild type and 5xFAD mice on the Morris water maze, from 3 to 15 months of age. The 5xFAD mice showed impaired learning at 6–9 months of age, but memory impairments were not detected with the test procedure used in this study. Performance of 5xFAD mice was profoundly impaired at 12–15 months of age, but was accompanied by slower swim speeds than wild-type mice and a frequent failure to locate the escape platform. Overall female mice performed worse than males, and reversal learning impairments in 5xFAD mice were more pronounced in females than males. Albino mice performed worse than pigmented mice, confirming that albinism can impair performance of 5xFAD mice independently of AD-related transgenes. Overall, these results show that 5xFAD mice have impaired learning performance at 6–9 months of age, but learning and memory performance at 12–15 months is confounded with motor impairments. Furthermore, sex and albinism should be controlled to provide an accurate assessment of AD-related transgenes on learning and memory. These results will help reduce variability across pre-clinical experiments with 5xFAD mice, and thus enhance the reliability of studies developing new therapeutics for AD.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/f3/GBB-21-e12794.PMC9744519.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10668077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}