Genes Brain and Behavior最新文献

{"title":"Genetic Propensity for Delay Discounting and Educational Attainment in Adults Are Associated With Delay Discounting in Preadolescents: Findings From the Adolescent Brain Cognitive Development Study","authors":"Jill A. Rabinowitz,&nbsp;Nathaniel Thomas,&nbsp;Justin C. Strickland,&nbsp;John J. Meredith,&nbsp;I-Tzu Hung,&nbsp;Renata B. Cupertino,&nbsp;Julia W. Felton,&nbsp;Brett Gelino,&nbsp;Bryant Stone,&nbsp;Brion S. Maher,&nbsp;Danielle Dick,&nbsp;Richard Yi,&nbsp;Victor Flores-Ocampo,&nbsp;Luis M. García-Marín,&nbsp;Miguel E. Rentería,&nbsp;Abraham A. Palmer,&nbsp;Sandra Sanchez-Roige","doi":"10.1111/gbb.70020","DOIUrl":"https://doi.org/10.1111/gbb.70020","url":null,"abstract":"<p>Higher delay discounting (DD) (i.e., propensity to devalue larger, delayed rewards over immediate, smaller rewards) is a transdiagnostic marker underpinning multiple health behaviors. Although genetic influences account for some of the variability in DD among adults, less is known about the genetic contributors to DD among preadolescents. We examined whether polygenic scores (PGS) for DD, educational attainment, and behavioral traits (i.e., impulsivity, inhibition, and externalizing behavior) were associated with phenotypic DD among preadolescents. Participants included youth (<i>N</i> = 8982, 53% male) from the Adolescent Brain Cognitive Development Study who completed an Adjusting Delay Discounting Task at the 1-year follow-up and had valid genetic data. PGS for DD, educational attainment, impulsivity, inhibition, and externalizing behaviors were created based on the largest GWAS available. Separate linear mixed effects models were conducted in individuals most genetically similar to European (EUR; <i>n</i> = 4972), African (AFR; <i>n</i> = 1769), and Admixed American (AMR; <i>n</i> = 2241) reference panels. After adjusting for age, sex, income, and the top ten genetic ancestry principal components, greater PGS for DD and lower educational attainment (but not impulsivity, inhibition, or externalizing) were associated with higher rates of DD (i.e., preference for sooner, smaller rewards) in participants most genetically similar to EUR reference panels. Findings provide insight into the influence of genetic propensity for DD and educational attainment on the discounting tendencies of preadolescents, particularly those most genetically similar to European reference samples, thereby advancing our understanding of the etiology of choice behaviors in this population.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717312","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":"Investigating Motor Coordination Using BXD Recombinant Inbred Mice to Model the Genetic Underpinnings of Developmental Coordination Disorder","authors":"Jeffy Rajan Soundara Rajan,&nbsp;Kamaldeep Gill,&nbsp;Eric Chow,&nbsp;David G. Ashbrook,&nbsp;Robert W. Williams,&nbsp;Jill G. Zwicker,&nbsp;Daniel Goldowitz","doi":"10.1111/gbb.70014","DOIUrl":"https://doi.org/10.1111/gbb.70014","url":null,"abstract":"<p>The fundamental skills for motor coordination and motor control emerge through development. Neurodevelopmental disorders such as developmental coordination disorder (DCD) lead to impaired acquisition of motor skills. This study investigated motor behaviors that reflect the core symptoms of human DCD through the use of BXD recombinant inbred strains of mice that are known to have divergent phenotypes in many behavioral traits, including motor activity. We sought to correlate behavior in basic motor control tasks with the known genotypes of these reference populations of mice using quantitative trait locus (QTL) mapping. We used 12 BXD strains with an average of 16 mice per group to assess the onset of reflexes during the early neonatal stage of life and differences in motor coordination using the tests for open field, rotarod, and gait behaviors during the adolescent/young adulthood period. Results indicated significant variability between strains in when neonatal reflexes appeared and significant strain differences for all measures of motor coordination. Five strains (BXD15, BXD27, BXD28, BXD75, BXD86) struggled with sensorimotor coordination as seen in gait analysis, rotarod, and open field, similar to human presentation of DCD. We identified three significant quantitative trait loci for gait on proximal Chr 3, Chr 4, and distal Chr 6. Based on expression, function, and polymorphism within the mapped QTL intervals, seven candidate genes (<i>Gpr63, Spata5, Trpc3, Cntn6, Chl1, Grm7, Ogg1</i>) emerged. This study offers new insights into mouse motor behavior, which promises to be a first murine model to explore the genetics and neural correlates of DCD.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595361","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 Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats","authors":"Christopher P. King,&nbsp;Apurva S. Chitre,&nbsp;Joel D. Leal-Gutiérrez,&nbsp;Jordan A. Tripi,&nbsp;Alesa H. Netzley,&nbsp;Aidan P. Horvath,&nbsp;Alexander C. Lamparelli,&nbsp;Anthony George,&nbsp;Connor Martin,&nbsp;Celine L. St. Pierre,&nbsp;Thiago Missfeldt Sanches,&nbsp;Hannah V. Bimschleger,&nbsp;Jianjun Gao,&nbsp;Riyan Cheng,&nbsp;Khai-Minh Nguyen,&nbsp;Katie L. Holl,&nbsp;Oksana Polesskaya,&nbsp;Keita Ishiwari,&nbsp;Hao Chen,&nbsp;Terry E. Robinson,&nbsp;Shelly B. Flagel,&nbsp;Leah C. Solberg Woods,&nbsp;Abraham A. Palmer,&nbsp;Paul J. Meyer","doi":"10.1111/gbb.70018","DOIUrl":"https://doi.org/10.1111/gbb.70018","url":null,"abstract":"<p>Addiction vulnerability is associated with the tendency to attribute incentive salience to reward predictive cues. Both addiction and the attribution of incentive salience are influenced by environmental and genetic factors. To characterize the genetic contributions to incentive salience attribution, we performed a genome-wide association study (GWAS) in a cohort of 1596 heterogeneous stock (HS) rats. Rats underwent a Pavlovian conditioned approach task that characterized the responses to food-associated stimuli (“cues”). Responses ranged from cue-directed “sign-tracking” behavior to food-cup directed “goal-tracking” behavior (12 measures, SNP heritability: 0.051–0.215). Next, rats performed novel operant responses for unrewarded presentations of the cue using the conditioned reinforcement procedure. GWAS identified 14 quantitative trait loci (QTLs) for 11 of the 12 traits across both tasks. Interval sizes of these QTLs varied widely. Seven traits shared a QTL on chromosome 1 that contained a few genes (e.g., <i>Tenm4</i>, <i>Mir708</i>) that have been associated with substance use disorders and other psychiatric disorders in humans. Other candidate genes (e.g., <i>Wnt11</i>, <i>Pak1</i>) in this region had coding variants and expression-QTLs in mesocorticolimbic regions of the brain. We also conducted a Phenome-Wide Association Study (PheWAS) on addiction-related behaviors in HS rats and found that the QTL on chromosome 1 was also associated with nicotine self-administration in a separate cohort of HS rats. These results provide a starting point for the molecular genetic dissection of incentive motivational processes and provide further support for a relationship between the attribution of incentive salience and drug abuse-related traits.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143564642","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":"Single-Nucleus RNA Sequencing Reveals Enduring Signatures of Acute Stress and Chronic Exercise in Striatal Microglia","authors":"Meghan G. Connolly,&nbsp;Zachary V. Johnson,&nbsp;Lynna Chu,&nbsp;Nicholas D. Johnson,&nbsp;Trevor J. Buhr,&nbsp;Elizabeth M. McNeill,&nbsp;Peter J. Clark,&nbsp;Justin S. Rhodes","doi":"10.1111/gbb.70019","DOIUrl":"https://doi.org/10.1111/gbb.70019","url":null,"abstract":"<p>Acute stress has enduring effects on the brain and motivated behavior across species. For example, acute stress produces persisting decreases in voluntary physical activity as well as molecular changes in the striatum, a brain region that regulates voluntary physical activity and other motivated behaviors. Microglia, the primary immune cells of the central nervous system, are positioned at the interface between neural responses to stress and neural coordination of voluntary activity in that they respond to stress, sense molecular changes in the striatum, and modulate neuronal activity. However, the role of striatal microglia in stress-induced long-term suppression of voluntary activity is unknown. Here, we employ single-nucleus RNA sequencing to investigate how stress and exercise impact the biology of microglia in the striatum. We find that striatal microglia display altered activation profiles 6 weeks after an acute stressor. Furthermore, we show that access to a running wheel is associated with an additional and distinct microglial activation profile characterized by upregulation of genes related to complement components and phagocytosis pathways. Finally, we find that distinct gene sets show expression changes associated with general access to a running wheel versus variation in running levels. Taken together, our results deepen our understanding of the diverse molecular states that striatal microglia assume in response to stress and exercise and suggest that microglia exhibit a broader range of functional states than previously thought.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554514","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":"Whole Genome Sequencing of Pedigrees With High Density of Substance Use and Psychiatric Disorders: A Meeting Report","authors":"Shirley Y. Hill,&nbsp;Howard J. Edenberg,&nbsp;Aiden Corvin,&nbsp;Thorgeir Thorgeirsson,&nbsp;Jennifer E. Below,&nbsp;David Goldman,&nbsp;Suzanne Leal,&nbsp;Laura Almasy,&nbsp;Nancy J. Cox,&nbsp;Mark Daly,&nbsp;Benjamin Neale,&nbsp;Scott Vrieze,&nbsp;Huda Zoghbi","doi":"10.1111/gbb.70017","DOIUrl":"https://doi.org/10.1111/gbb.70017","url":null,"abstract":"<p>The National Institute of Drug Abuse convened a panel of scientists with expertise in substance use disorders (SUD) and genetic methodologies primarily to determine the feasibility of performing whole genome sequencing utilizing existing pedigree collections with a high density of SUD and psychiatric disorders. A major focus was on determining if there had been any successes in identifying genetic variants for complex traits in family-based designs. Such information could provide assurance that whole genome sequencing might provide significant pay-offs particularly in the pursuit of rare variants and copy number variants. An important goal was to discuss and evaluate optimal strategies for studying genetic variants in human samples. Specific topics were (a) to consider whether a smaller number of cases typically available in family studies versus the larger number available in biobanks can reveal unique information; (b) to identify potential gaps in information available in biobank data that might be supplemented with family data; (c) to consider the optimal SUD phenotypic definitions (e.g., quantity of use, problem-oriented) and data collection instruments (self-report or clinician administered) that are both practical and efficient to collect, and likely to provide important insights concerning prevention, intervention, and medication development. Conclusions reached by the panel included optimism about the successes that have occurred in the existing family studies ascertained to include densely affected pedigrees. Evaluation of methodologies led, overall, to a panel consensus that steps should be taken to utilize biobank collection in conjunction with family-based investigations for optimal variant discovery.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389180","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":"The Roles of Discrete Populations of Neurons Expressing Short Neuropeptide F in Sleep Induction in Drosophila melanogaster","authors":"Jamie M. Stonemetz,&nbsp;Nikoleta Chantzi,&nbsp;Emily L. Perkins,&nbsp;Aaliyah J. Peralta,&nbsp;Debra R. Possidente,&nbsp;John P. Tagariello,&nbsp;Marryn M. Bennett,&nbsp;Hooralain Alnassar,&nbsp;Andrew M. Dacks,&nbsp;Christopher G. Vecsey","doi":"10.1111/gbb.70010","DOIUrl":"https://doi.org/10.1111/gbb.70010","url":null,"abstract":"<p>Sleep is of vital importance in our lives, yet we are far from understanding the neuronal networks that control the amount and timing of sleep. There is substantial conservation of known sleep-regulating transmitters, allowing for studies in simpler organisms to lead the way in gaining insight into the organization of sleep control circuits. In <i>Drosophila melanogaster</i>, we recently showed that optogenetic activation of neurons that produce the neuropeptide Y (NPY)-related transmitter short neuropeptide F (sNPF) increases time spent asleep. However, sNPF is expressed in several neuronal populations, and thus it is unknown which of those populations play roles in the sleep-promoting effect. In this study, we addressed this issue using a genetic approach to limit optogenetic activation to subsets of sNPF-expressing neurons. We found that sleep promotion was shorter-lived when cryptochrome (CRY)-positive neurons were excluded from being activated. Pigment-dispersing factor (PDF) neurons were not required for sleep promotion, nor were mushroom body (MB) neurons. Acute reactions to a short, 10-s period of optogenetic activation were largely unchanged by excluding activation of the three neuronal populations mentioned above. Together, these results suggest that clock neurons that are CRY-positive and PDF-negative are important contributors to the long-lasting sleep promotion produced by sNPF neuron activation. However, other neurons targeted by the sNPF-GAL4 driver appear to mediate the more rapid behavioral responses. Future studies will seek to identify these additional sNPF neuron populations and to determine how sNPF-expressing clock neurons act in concert with other neuronal circuits to promote sleep.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362831","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":"More and Less Fear in Serotonin Transporter Knockout Mice","authors":"João Lima,&nbsp;Marios C. Panayi,&nbsp;Trevor Sharp,&nbsp;Stephen B. McHugh,&nbsp;David M. Bannerman","doi":"10.1111/gbb.70016","DOIUrl":"https://doi.org/10.1111/gbb.70016","url":null,"abstract":"<p>Recent theories suggest that reduced serotonin transporter (5-HTT) function, which increases serotonin (5-HT) levels at the synapse, enhances neural plasticity and affects sensitivity to environmental cues. This may promote learning about emotionally relevant events. However, the boundaries that define such emotional learning remain to be established. This was investigated using 5-HTT knockout (5-HTTKO) mice which provide a model of long-term elevated 5-HT transmission and are associated with increased anxiety. Compared to wild-type controls, 5-HTTKO mice were faster to discriminate between an auditory cue that predicted footshock (CS+) and a cue predicting no footshock (CS−). Notably, this enhanced discrimination performance was driven not by faster learning that the CS+ predicted footshock, but rather by faster learning that the CS− cue signals the absence of footshock and thus provides temporary relief from fear/anxiety. Similarly, 5-HTTKO mice were also faster to reduce their fear of the CS+ cue during subsequent extinction. These findings are consistent with facilitated inhibitory learning that predicts the absence of potential threats in 5-HTTKO mice. However, 5-HTTKO mice also exhibited increased generalisation of fear learning about ambiguous aversive cues in a novel context, different from the training context. Thus, 5-HTTKO mice can exhibit both more and less fear compared to wild-type controls. Taken together, our results support the idea that loss of 5-HTT function, and corresponding increases in synaptic 5-HT availability, may facilitate learning by priming of aversive memories. This both facilitates inhibitory learning for fear memories but also enhances generalisation of fear.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362832","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":"Distinct Effects of Olanzapine Depot Treatment on Behavior and Muscarinic M1 Receptor Expression in the Triple-Hit Wisket Rat Model of Schizophrenia","authors":"Gyongyi Horvath,&nbsp;Eszter Ducza,&nbsp;Leatitia Gabriella Adlan,&nbsp;Alexandra Büki,&nbsp;Gabriella Kekesi","doi":"10.1111/gbb.70015","DOIUrl":"10.1111/gbb.70015","url":null,"abstract":"<p>This study aimed to characterize the triple-hit schizophrenia-like model rats (Wisket) by the assessment of (1) behavioral parameters in different test conditions (reward-based Ambitus test and HomeManner system) for a prolonged period, (2) cerebral muscarinic M1 receptor (M1R) expression, and (3) the effects of olanzapine treatment on these parameters. Wistar (control) and Wisket rats were injected for three consecutive weeks with olanzapine depot (100 mg/kg) and spent 4 weeks in large cages with environmental enrichment (HomeManner). The vehicle-treated Wisket rats spent longer time awake with decreased grooming activity compared to controls, without changes in their active social behavior (sniffing, playing, fighting) obtained in HomeManner. Olanzapine treatment decreased most of these parameters, only the passive social interaction (huddling during sleeping) enhanced mostly in the Wisket rats on the injection day, which recovered within 4 days. In the Ambitus test, vehicle-treated Wisket rats showed lower locomotor and exploratory activities and impaired cognition compared to control rats, deteriorating by olanzapine in both groups. In Wisket brain samples, the M1R mRNA expression was significantly lower in the cerebral cortex and elevated in the hippocampus, with no difference in the prefrontal cortex versus control. Olanzapine normalized the hippocampal M1R expression, but enhanced it in the prefrontal cortex. The triple-hit Wisket model rats had impaired behavioral characteristics in both acute reward-based test and undisturbed circumstances investigated for prolonged periods, and altered cerebral M1R expression. Chronic olanzapine treatment resulted deterioration of some parameters in control group, and could restore only few negative signs in model rats.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025736","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":"Atp1a2 and Kcnj9 Are Candidate Genes Underlying Sensitivity to Oxycodone-Induced Locomotor Activation and Withdrawal-Induced Anxiety-Like Behaviors in C57BL/6 Substrains","authors":"Lisa R. Goldberg,&nbsp;Britahny M. Baskin,&nbsp;Jacob A. Beierle,&nbsp;Yahia Adla,&nbsp;Julia C. Kelliher,&nbsp;Emily J. Yao,&nbsp;Stacey L. Kirkpatrick,&nbsp;Eric R. Reed,&nbsp;David F. Jenkins,&nbsp;Jiayi Cox,&nbsp;Alexander M. Luong,&nbsp;Kimberly P. Luttik,&nbsp;Julia A. Scotellaro,&nbsp;Timothy A. Drescher,&nbsp;Sydney B. Crotts,&nbsp;Neema Yazdani,&nbsp;Martin T. Ferris,&nbsp;W. Evan Johnson,&nbsp;Megan K. Mulligan,&nbsp;Camron D. Bryant","doi":"10.1111/gbb.70009","DOIUrl":"10.1111/gbb.70009","url":null,"abstract":"<p>Opioid use disorder is heritable, yet its genetic etiology is largely unknown. C57BL/6J and C57BL/6NJ mouse substrains exhibit phenotypic diversity in the context of limited genetic diversity which together can facilitate genetic discovery. Here, we found C57BL/6NJ mice were less sensitive to oxycodone (OXY)-induced locomotor activation versus C57BL/6J mice in a conditioned place preference paradigm. Narrow-sense heritability of OXY-induced locomotor activity traits ranged from 0.22 to 0.31, implicating suitability for genetic analysis. Quantitative trait locus (QTL) mapping in an F2 cross identified a chromosome 1 QTL explaining 7%–12% of the variance in OXY locomotion and anxiety-like withdrawal in the elevated plus maze. A second QTL for EPM withdrawal behavior on chromosome 5 near <i>Gabra2</i> (alpha-2 subunit of GABA-A receptor) explained 9% of the variance. To narrow the chromosome 1 locus, we generated recombinant lines spanning 163–181 Mb, captured the QTL for OXY locomotor traits and withdrawal, and fine-mapped a 2.45-Mb region (170.16–172.61 Mb). Transcriptome analysis identified five, localized striatal cis-eQTL transcripts and two were confirmed at the protein level (KCNJ9, ATP1A2). <i>Kcnj9</i> codes for a potassium channel (GIRK3) that is a major effector of mu opioid receptor signaling. <i>Atp1a2</i> codes for a subunit of a Na+/K+ ATPase enzyme that regulates neuronal excitability and shows functional adaptations following chronic opioid administration. To summarize, we identified two candidate genes underlying the physiological and behavioral properties of opioids, with direct preclinical relevance to investigators employing these widely used substrains and clinical relevance to human genetic studies of opioid use disorder.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973120","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":"Understanding the Emergence of Schizophrenia in the Light of Human Evolution: New Perspectives in Genetics","authors":"Veronica Sandroni,&nbsp;Boris Chaumette","doi":"10.1111/gbb.70013","DOIUrl":"10.1111/gbb.70013","url":null,"abstract":"<p>Schizophrenia is a frequent and disabling disease. The persistence of the disorder despite its harmful consequences represents an evolutionary paradox. Based on recent discoveries in genetics, scientists have formulated the “price-to-pay” hypothesis: schizophrenia would be intimately related to human evolution, particularly to brain development and human-specific higher cognitive functions. The objective of the present work is to question scientific literature about the relationship between schizophrenia and human evolution from a genetic point of view. In the last two decades, research investigated the association between schizophrenia and a few genetic evolutionary markers: Human accelerated regions, segmental duplications, and highly repetitive DNA such as the Olduvai domain. Other studies focused on the action of natural selection on schizophrenia-associated genetic variants, also thanks to the complete sequencing of archaic hominins' genomes (Neanderthal, Denisova). Results suggested that a connection between human evolution and schizophrenia may exist; nonetheless, much research is still needed, and it is possible that a definitive answer to the evolutionary paradox of schizophrenia will never be found.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973122","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}