Genes Brain and Behavior最新文献

{"title":"A Mutation in the Transmembrane Domain of Adenylate Cyclase 3 Impairs Enzymatic Function to Cause Sex-Specific Depression- and Anxiety-Like Behaviors and Food Seeking in a Rat Model","authors":"Mackenzie K. Fitzpatrick,&nbsp;Christina Dyson,&nbsp;Angela Beeson,&nbsp;Leighelle Adrian,&nbsp;Glen Marrs,&nbsp;Michael Grzybowski,&nbsp;Jason Klotz,&nbsp;Aron M. Geurts,&nbsp;Rong Chen,&nbsp;Jeffrey L. Weiner,&nbsp;Leah C. Solberg Woods","doi":"10.1111/gbb.70028","DOIUrl":"https://doi.org/10.1111/gbb.70028","url":null,"abstract":"<p>We have previously demonstrated that a transmembrane domain mutation in <i>Adenylate cyclase 3</i> (<i>Adcy3</i>) causes increased adiposity and negative emotion-like behaviors in a rat model. We set out to replicate and expand upon our previous study by conducting comprehensive behavioral testing, and we also investigated the molecular changes that result from this mutation. Rats with a mutation in the second transmembrane helix of ADCY3 (Adcy3^mut/mut) and wild-type rats were fed a high-fat diet for 12 weeks. We measured body weight, body composition, and depression-like and anxiety-like behaviors using the following tests: sucrose splash test, sucrose preference test, forced swim test, open field test, elevated plus maze, successive alleys test, and novelty-suppressed feeding. We also measured serum leptin levels, hypothalamic cyclic AMP (cAMP) production, and membrane fraction ADCY3 content. Adcy3^mut/mut male and female rats had increased adiposity. Adcy3^mut/mut males showed increased despair- and anxiety-like behaviors, food seeking, and higher leptin levels relative to wild-type males. Adcy3^mut/mut females showed only mildly increased anxiety-like behaviors relative to wild-type females. Adcy3^mut/mut rats of both sexes had decreased cAMP production in the hypothalamus, with no changes in ADCY3 content in the membrane fraction. We conclude that the transmembrane domain of ADCY3 plays a critical role in regulating adiposity and behavior, as well as cAMP production. There were key differences between males and females for the observed phenotypes. This study supports the idea that <i>Adcy3</i> contributes to emotion-like behaviors and potentially mental health disorders, and that the transmembrane domain of ADCY3 is important for protein function.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244659","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":"Preliminary Insights Into the Relationship Between the Gut Microbiome and Host Genome in Posttraumatic Stress Disorder","authors":"Michaela A. O'Hare,&nbsp;Carlien Rust,&nbsp;Stefanie Malan-Müller,&nbsp;Walter Pirovano,&nbsp;Christopher A. Lowry,&nbsp;Matsepo Ramaboli,&nbsp;Leigh L. van den Heuvel,&nbsp;Soraya Seedat,&nbsp;PGC-PTSD Microbiome Workgroup,&nbsp;Sian M. J. Hemmings","doi":"10.1111/gbb.70025","DOIUrl":"https://doi.org/10.1111/gbb.70025","url":null,"abstract":"<p>Posttraumatic stress disorder (PTSD) may develop following trauma exposure; however, not all trauma-exposed individuals develop PTSD, suggesting the presence of susceptibility and resilience factors. The gut microbiome and host genome, which are interconnected, have been implicated in the aetiology of PTSD. However, their interaction has yet to be investigated in a South African population. Using genome-wide genotype data and 16S rRNA (V4) gene amplicon sequencing data from 53 trauma-exposed controls and 74 PTSD cases, we observed no significant association between the host genome and summed abundance of <i>Mitsuokella, Odoribacter, Catenibacterium</i> and <i>Olsenella</i>, previously reported as associated with PTSD status in this cohort. However, <i>PROM2</i> rs2278067 T-allele was significantly positively associated with the summed relative abundance of these genera, but only in individuals with PTSD and not trauma-exposed controls (<i>p</i> &lt; 0.014). Polygenic risk scores generated using genome-wide association study summary statistics from the PGC-PTSD Overall Freeze 2 were not predictive of gut microbial composition in this cohort. These preliminary results suggest a potential role for the interaction between genetic variation and gut microbial composition in the context of PTSD, underscoring the need for further investigation.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245065","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":"Impaired Cognitive Flexibility With Preserved Learning in an Amyloid Precursor Protein Knock-In Mouse Model of Amyloidopathy","authors":"Julie R. Dumont,&nbsp;Paul A. S. Sheppard,&nbsp;Chris Fodor,&nbsp;M. Alexander Coto,&nbsp;Sabrina Yang,&nbsp;Takashi Saito,&nbsp;Takaomi C. Saido,&nbsp;R. Jane Rylett,&nbsp;Marco A. M. Prado,&nbsp;Timothy J. Bussey,&nbsp;Lisa M. Saksida,&nbsp;Vania F. Prado","doi":"10.1111/gbb.70024","DOIUrl":"https://doi.org/10.1111/gbb.70024","url":null,"abstract":"<p>Alzheimer's disease is a debilitating neurodegenerative condition characterized by amyloid beta plaques and tau neurofibrillary tangles, which leads to progressive cognitive decline. Several new mouse models of fast amyloid deposition have been generated with compound mutations, but how these affect high-level cognitive function is still not fully understood. Four cohorts of a second-generation amyloid precursor protein knock-in mouse model, <i>App</i>^{NL-G-F/NL-G-F}, which develops aggressive amyloidopathy, were compared with two different control groups that do not produce plaques (<i>App</i>^NL/NL and wildtype littermates), on touchscreen-based tests of learning and cognitive flexibility. <i>App</i>^{NL-G-F/NL-G-F} mice learned to discriminate between two visual stimuli during the pairwise visual discrimination (PVD) task but were impaired when the reward contingencies were reversed (the PVR task). Analyses of the correction trials indicated perseverative behavior. One cohort was further tested on the touchscreen Extinction test, which isolates the ability to withhold responding to a previously rewarded stimulus. The <i>App</i>^{NL-G-F/NL-G-F} mice extinguished their responding no differently than the <i>App</i>^NL/NL control group. These results indicate that compound mutations in <i>App</i> driving fast accumulation of plaques in this mouse model impair cognitive flexibility and may serve as a preclinical target for putative therapeutic drugs.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197516","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":"Vitamin C Transport Deficiency Alters Striatal Dopamine Gene Expression and Metabolism in YAC128 Huntington Disease Mice","authors":"Adriana A. Tienda,&nbsp;Fiona E. Harrison,&nbsp;Jordyn M. Wilcox","doi":"10.1111/gbb.70023","DOIUrl":"https://doi.org/10.1111/gbb.70023","url":null,"abstract":"<p>Neurodegeneration in Huntington disease (HD) contributes to dopaminergic system dysfunction via the loss of striatal medium spiny neurons expressing dopamine receptors. Given the key role for ascorbic acid (vitamin C) in dopamine synthesis and neurotransmission, we investigated whether mild cellular ascorbate deficiency accelerates dopaminergic dysfunction in the development of HD pathology and behavioral deficits. YAC128 mice expressing mutant human huntingtin were crossed with SVCT2^+/− mice, which carry a heterozygous knockout of the sodium-dependent vitamin C transporter, to generate mice with approximately 30% decreased neuronal vitamin C as well as progressive changes in dopamine signaling. Behavioral and neurochemical outcomes were assessed at early disease stages. At 14 and 20 weeks, YAC128 and SVCT2^+/− YAC128 mice showed similar deficits in grip strength, locomotor activity, and rotarod performance compared to controls, suggesting modest ascorbate deficiency did not accelerate motor phenotypes. Gene expression analysis revealed six significantly upregulated genes in the striatum of SVCT2^+/− YAC128 mice, including those involved in dopamine synthesis, packaging, and transport. Notably, striatal dopamine and serotonin and their metabolites were decreased in both single mutant mouse lines (YAC128 and SVCT2^+/−) but without a compounding effect of the double mutation (SVCT2^+/− YAC128). These results indicate that while moderate ascorbate deficiency may not worsen early behavioral phenotypes in the YAC128 model, it does impact dopamine system regulation at the molecular level. These findings highlight the potential importance of ascorbate in modifying disease progression and suggest that humans with HD, who cannot synthesize ascorbate, may be particularly vulnerable to vitamin C deficiency effects on dopamine dynamics.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148441","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":"Reduced Cacna1c Expression Produces Anhedonic Reactions to Palatable Sucrose in Rats: No Interactions With Juvenile or Adult Stress","authors":"Patricia Gasalla,&nbsp;Kerrie L. Thomas,&nbsp;Lawrence Wilkinson,&nbsp;Jeremy Hall,&nbsp;Dominic Michael Dwyer","doi":"10.1111/gbb.70021","DOIUrl":"https://doi.org/10.1111/gbb.70021","url":null,"abstract":"<p>Genetic variation in <i>CACNA1C</i>, which encodes the alpha-1 subunit of Ca_v1.2 L-type voltage-gated calcium channels, is strongly linked to risk for psychiatric disorders including schizophrenia, bipolar disorder, and major depression. Here we investigated the impact of mutations of one copy of <i>Cacna1c</i> (leading to low gene dosage of <i>Cacna1c</i>) on rats' hedonic responses to palatable sucrose (assessed using the analysis of consumption microstructure). In addition, we also investigated the effects of combining either juvenile or adult stress with the manipulation of <i>Cacna1c</i>. Across three experiments, <i>Cacna1c</i>^+/− rats displayed attenuated hedonic reactions to sucrose compared to wild-type littermate controls, despite the <i>Cacna1c</i>^+/− rats retaining sensitivity to sucrose concentration in terms of the amount of consumption. Unexpectedly, juvenile stress enhanced rather than reduced hedonic reactions to sucrose, while adult stress did not have clear hedonic effects. The effects of <i>Cacna1c</i> manipulation did not interact with either juvenile or adult stress. The fact that <i>Cacna1c</i>^+/− rats display a clear analogue of anhedonia—a reduction in the positive hedonic reactions normally elicited by highly palatable sucrose—a symptom observed trans-diagnostically across psychiatric disorders linked to <i>CACNA1C</i>, suggests this model may play a valuable role in the translational investigation of anhedonia.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861681","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":"Expression of GDAP1 Gene Correlates With Alcohol Deprivation Effect","authors":"Rona Yarimay,&nbsp;Dominik K. E. Beyer,&nbsp;Annakarina Mundorf,&nbsp;Nadja Freund","doi":"10.1111/gbb.70022","DOIUrl":"https://doi.org/10.1111/gbb.70022","url":null,"abstract":"<p>Alcohol addiction is a widespread disease, and the exact causes and consequences are still not fully determined. Neurotransmitters and neuronal circuits are not only the target structure of alcohol and responsible for its direct effects but also play a central role in the development of addiction. A gene that has been linked to alcohol use disorder in recent studies is the <i>ganglioside-induced differentiation-associated protein 1 (GDAP1)</i> gene. The present study focuses on the hippocampus, a brain region particularly vulnerable to alcohol and rich in <i>Gdap1</i> gene expression. Using an established drinking model, alcohol drinking behavior was induced in adult male Long Evans rats. After 6 weeks of voluntary alcohol intake, followed by 2 weeks of deprivation, the animals were divided into two groups based on the alcohol deprivation effect (ADE). <i>Gdap1</i> gene expression was measured with real-time PCR in the hippocampus. Results reveal significantly decreased mRNA expression in the high ADE group compared to the low ADE group. This decrease was specifically detected within the cornu ammonis 3 (CA3) region. <i>Gdap1</i> expression in this region also negatively correlated with ADE in all animals. Taken together, results indicate that <i>Gdap1</i> might not only be associated with alcohol consumption but might even play a role in alcohol dependence.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849247","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 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}