Genes Brain and Behavior最新文献_第9页

The Drosophila dopamine 2-like receptor D2R (Dop2R) is required in the blood brain barrier for male courtship 果蝇多巴胺2样受体D2R (Dop2R)是雄性求偶所需的血脑屏障

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2023-01-13 DOI: 10.1111/gbb.12836

Cameron R. Love, Sumit Gautam, Chamala Lama, Nhu Hoa Le, Brigitte Dauwalder

引用次数: 3

ChAT::Cre transgenic rats show sex-dependent altered fear behaviors, ultrasonic vocalizations and cholinergic marker expression ChAT: Cre转基因大鼠表现出性别依赖性的恐惧行为、超声发声和胆碱能标记物表达的改变

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2023-01-13 DOI: 10.1111/gbb.12837

Sarah C. Tryon, Iris M. Sakamoto, Kris F. Kaigler, Gabriella Gee, Jarrett Turner, Katherine Bartley, Jim R. Fadel, Marlene A. Wilson

{"title":"ChAT::Cre transgenic rats show sex-dependent altered fear behaviors, ultrasonic vocalizations and cholinergic marker expression","authors":"Sarah C. Tryon, Iris M. Sakamoto, Kris F. Kaigler, Gabriella Gee, Jarrett Turner, Katherine Bartley, Jim R. Fadel, Marlene A. Wilson","doi":"10.1111/gbb.12837","DOIUrl":"10.1111/gbb.12837","url":null,"abstract":"The cholinergic system is a critical regulator of Pavlovian fear learning and extinction. As such, we have begun investigating the cholinergic system's involvement in individual differences in cued fear extinction using a transgenic ChAT::Cre rat model. The current study extends behavioral phenotyping of a transgenic ChAT::Cre rat line by examining both freezing behavior and ultrasonic vocalizations (USVs) during a Pavlovian cued fear learning and extinction paradigm. Freezing, 22 kHz USVs, and 50 kHz USVs were compared between male and female transgenic ChAT::Cre+ rats and their wildtype (Cre-) littermates during fear learning, contextual and cue-conditioned fear recall, cued fear extinction, and generalization to a novel tone. During contextual and cued fear recall ChAT::Cre+ rats froze slightly more than their Cre- littermates, and displayed significant sex differences in contextual and cue-conditioned freezing, 22 kHz USVs, and 50 kHz USVs. Females showed more freezing than males in fear recall trials, but fewer 22 kHz distress calls during fear learning and recall. Females also produced more 50 kHz USVs during exposure to the testing chambers prior to tone (or shock) presentation compared with males, but this effect was blunted in ChAT::Cre+ females. Corroborating previous studies, ChAT::Cre+ transgenic rats overexpressed vesicular acetylcholine transporter immunolabeling in basal forebrain, striatum, basolateral amygdala, and hippocampus, but had similar levels of acetylcholinesterase and numbers of ChAT+ neurons as Cre- rats. This study suggests that variance in behavior between ChAT::Cre+ and wildtype rats is sex dependent and advances theories that distinct neural circuits and processes regulate sexually divergent fear responses.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/dd/GBB-22-e12837.PMC9994175.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9073397","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}

引用次数: 0

Hippocampal RNA sequencing in mice selectively bred for high and low activity 选择性培育高活性和低活性小鼠的海马RNA测序。

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2022-12-13 DOI: 10.1111/gbb.12832

Winona C. Booher, Lauren A. Vanderlinden, Lucy A. Hall, Aimee L. Thomas, Luke M. Evans, Laura M. Saba, Marissa A. Ehringer

{"title":"Hippocampal RNA sequencing in mice selectively bred for high and low activity","authors":"Winona C. Booher, Lauren A. Vanderlinden, Lucy A. Hall, Aimee L. Thomas, Luke M. Evans, Laura M. Saba, Marissa A. Ehringer","doi":"10.1111/gbb.12832","DOIUrl":"10.1111/gbb.12832","url":null,"abstract":"High and Low Activity strains of mice were bidirectionally selected for differences in open-field activity (DeFries et al., 1978, Behavior Genetics, 8: 3–13) and subsequently inbred to use as a genetic model for studying anxiety-like behaviors (Booher et al., 2021, Genes, Brain and Behavior, 20: e12730). Hippocampal RNA-sequencing of the High and Low Activity mice identified 3901 differentially expressed protein-coding genes, with both sex-dependent and sex-independent effects. Functional enrichment analysis (PANTHER) highlighted 15 gene ontology terms, which allowed us to create a narrow list of 264 top candidate genes. Of the top candidate genes, 46 encoded four Complexes (I, II, IV and V) and two electron carriers (cytochrome c and ubiquinone) of the mitochondrial oxidative phosphorylation process. The most striking results were in the female high anxiety, Low Activity mice, where 39/46 genes relating to oxidative phosphorylation were upregulated. In addition, comparison of our top candidate genes with two previously curated High and Low Activity gene lists highlight 24 overlapping genes, where Ndufa13, which encodes the supernumerary subunit A13 of complex I, was the only gene to be included in all three lists. Mitochondrial dysfunction has recently been implicated as both a cause and effect of anxiety-related disorders and thus should be further explored as a possible novel pharmaceutical treatment for anxiety disorders.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12832","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9255581","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}

引用次数: 0

TTLL11 gene is associated with sustained attention performance and brain networks: A genome-wide association study of a healthy Chinese sample TTLL11基因与持续注意力表现和大脑网络相关:一项健康中国人样本的全基因组关联研究

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2022-12-13 DOI: 10.1111/gbb.12835

Hejun Liu, Xiaoyu Zhao, Gui Xue, Chuansheng Chen, Qi Dong, Xuping Gao, Li Yang, Chunhui Chen

{"title":"TTLL11 gene is associated with sustained attention performance and brain networks: A genome-wide association study of a healthy Chinese sample","authors":"Hejun Liu, Xiaoyu Zhao, Gui Xue, Chuansheng Chen, Qi Dong, Xuping Gao, Li Yang, Chunhui Chen","doi":"10.1111/gbb.12835","DOIUrl":"10.1111/gbb.12835","url":null,"abstract":"Genetic studies on attention have mainly focused on children with attention-deficit/hyperactivity disorder (ADHD), so little systematic research has been conducted on genetic correlates of attention performance and their potential brain mechanisms among healthy individuals. The current study included a genome-wide association study (GWAS, N = 1145 healthy young adults) aimed to identify genes associated with sustained attention and an imaging genetics study (an independent sample of 483 healthy young adults) to examine any identified genes' influences on brain function. The GWAS found that TTLL11 showed genome-wide significant associations with sustained attention, with rs13298112 as the most significant SNP and the GG homozygotes showing more impulsive but also more focused responses than the A allele carriers. A retrospective examination of previously published ADHD GWAS results confirmed an un-reported, small but statistically significant effect of TTLL11 on ADHD. The imaging genetics study replicated this association and showed that the TTLL11 gene was associated with resting state activity and connectivity of the somatomoter network, and can be predicted by dorsal attention network connectivity. Specifically, the GG homozygotes showed lower brain activity, weaker brain network connectivity, and non-significant brain-attention association compared to the A allele carriers. Expression database showed that expression of this gene is enriched in the brain and that the G allele is associated with lower expression level than the A allele. These results suggest that TTLL11 may play a major role in healthy individuals' attention performance and may also contribute to the etiology of ADHD.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3d/2d/GBB-22-e12835.PMC9994169.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9134739","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}

引用次数: 0

A genome-wide association study identifies a new variant associated with word reading fluency in Chinese children 一项全基因组关联研究发现了一个与中国儿童单词阅读流利性相关的新变异

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2022-12-13 DOI: 10.1111/gbb.12833

Zhengjun Wang, Shunan Zhao, Liming Zhang, Qing Yang, Chen Cheng, Ning Ding, Zijian Zhu, Hua Shu, Chunyu Liu, Jingjing Zhao

{"title":"A genome-wide association study identifies a new variant associated with word reading fluency in Chinese children","authors":"Zhengjun Wang, Shunan Zhao, Liming Zhang, Qing Yang, Chen Cheng, Ning Ding, Zijian Zhu, Hua Shu, Chunyu Liu, Jingjing Zhao","doi":"10.1111/gbb.12833","DOIUrl":"10.1111/gbb.12833","url":null,"abstract":"Reading disability exhibited defects in different cognitive domains, including word reading fluency, word reading accuracy, phonological awareness, rapid automatized naming and morphological awareness. To identify the genetic basis of Chinese reading disability, we conducted a genome-wide association study (GWAS) of the cognitive traits related to Chinese reading disability in 2284 unrelated Chinese children. Among the traits analyzed in the present GWAS, we detected one genome-wide significant association (p < 5 × 10−8) on word reading fluency for one SNP on 4p16.2, within EVC genes (rs6446395, p = 7.33 × 10−10). Rs6446395 also showed significant association with Chinese character reading accuracy (p = 2.95 × 10−4), phonological awareness (p = 7.11 × 10−3) and rapid automatized naming (p = 4.71 × 10−3), implying multiple effects of this variant. The eQTL data showed that rs6446395 affected EVC expression in the cerebellum. Gene-based analyses identified a gene (PRDM10) to be associated with word reading fluency at the genome-wide level. Our study discovered a new candidate susceptibility variant for reading ability and provided new insights into the genetics of developmental dyslexia in Chinese children.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b4/78/GBB-22-e12833.PMC9994172.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9082098","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}

引用次数: 2

Genome-wide assessment reveals a significant association between ACSS3 and physical activity 全基因组评估揭示了ACSS3与身体活动之间的显著关联

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2022-12-12 DOI: 10.1111/gbb.12834

Jinyeon Jo, Youngkyu Song, Dankyu Yoon, Chung Gun Lee, Sungho Won

{"title":"Genome-wide assessment reveals a significant association between ACSS3 and physical activity","authors":"Jinyeon Jo, Youngkyu Song, Dankyu Yoon, Chung Gun Lee, Sungho Won","doi":"10.1111/gbb.12834","DOIUrl":"10.1111/gbb.12834","url":null,"abstract":"Recent genetic studies have identified physical activity (PA)-susceptible loci in European ancestry subjects; however, due to considerable genetic differences, these findings are not likely extendable to East Asian populations. Therefore, the present study aimed to identify significantly associated PA-susceptible loci using genome-wide association studies (GWASs) with East Asian (EAS) subjects and to generalize the findings to European (EUR) ancestries. The mRNA levels of genes located near the genome-wide significantly associated single-nucleotide polymorphisms (SNP) were compared under PA and control conditions. Rs74937256, located in ACSS3 (chromosome 12), which primarily functions in skeletal muscle tissues, was identified as a genome-wide significant variant (P = 6.06 × 10−9) in EAS. Additionally, the rs2525840, also in ACSS3 satisfied the Bonferroni corrected significance (P = 3.77 × 10−5) in EUR. We found that rs74937256 is an expressed trait locus of ACSS3 (P = 10−4), and ACSS3 mRNA expression significantly differs after PA, based on PrediXcan (P = 7 × 10−8) and the gene expression omnibus database (P = 0.043).","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2c/36/GBB-22-e12834.PMC9994161.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9134738","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}

引用次数: 0

Neuropathic pain as a trigger for histone modifications in limbic circuitry 神经性疼痛是边缘回路中组蛋白修饰的触发因素

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2022-11-22 DOI: 10.1111/gbb.12830

Svetlana Bryant, Julie-Anne Balouek, Luke T. Geiger, David J. Barker, Catherine J. Peña

{"title":"Neuropathic pain as a trigger for histone modifications in limbic circuitry","authors":"Svetlana Bryant, Julie-Anne Balouek, Luke T. Geiger, David J. Barker, Catherine J. Peña","doi":"10.1111/gbb.12830","DOIUrl":"10.1111/gbb.12830","url":null,"abstract":"Chronic pain involves both central and peripheral neuronal plasticity that encompasses changes in the brain, spinal cord, and peripheral nociceptors. Within the forebrain, mesocorticolimbic regions associated with emotional regulation have recently been shown to exhibit lasting gene expression changes in models of chronic pain. To better understand how such enduring transcriptional changes might be regulated within brain structures associated with processing of pain or affect, we examined epigenetic modifications involved with active or permissive transcriptional states (histone H3 lysine 4 mono and trimethylation, and histone H3 lysine 27 acetylation) in periaqueductal gray (PAG), lateral hypothalamus (LH), nucleus accumbens (NAc), and ventral tegmental area (VTA) 5 weeks after sciatic nerve injury in mice to model chronic pain. For both male and female mice in chronic pain, we observed an overall trend for a reduction of these epigenetic markers in periaqueductal gray, LH, and NAc, but not VTA. Moreover, we discovered that some epigenetic modifications exhibited changes associated with pain history, while others were associated with individual differences in pain sensitivity. When taken together, these results suggest that nerve injury leads to chronic chromatin-mediated suppression of transcription in key limbic brain structures and circuits, which may underlie enduring changes in pain processing and sensitivity within these systems.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/24/a1/GBB-22-e12830.PMC9994138.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9432170","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}

引用次数: 1

Allele-specific cis-regulatory methylation of the gene for vasoactive intestinal peptide in white-throated sparrows 白喉麻雀血管活性肠肽基因等位基因特异性顺式调控甲基化

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2022-10-11 DOI: 10.1111/gbb.12831

Mackenzie R. Prichard, Kathleen E. Grogan, Jennifer R. Merritt, Jessica Root, Donna L. Maney

{"title":"Allele-specific cis-regulatory methylation of the gene for vasoactive intestinal peptide in white-throated sparrows","authors":"Mackenzie R. Prichard, Kathleen E. Grogan, Jennifer R. Merritt, Jessica Root, Donna L. Maney","doi":"10.1111/gbb.12831","DOIUrl":"10.1111/gbb.12831","url":null,"abstract":"White-throated sparrows (Zonotrichia albicollis) offer a unique opportunity to connect genotype with behavioral phenotype. In this species, a rearrangement of the second chromosome is linked with territorial aggression; birds with a copy of this “supergene” rearrangement are more aggressive than those without it. The supergene has captured the gene VIP, which encodes vasoactive intestinal peptide, a neuromodulator that drives aggression in other songbirds. In white-throated sparrows, VIP expression is higher in the anterior hypothalamus of birds with the supergene than those without it, and expression of VIP in this region predicts the level of territorial aggression regardless of genotype. Here, we aimed to identify epigenetic mechanisms that could contribute to differential expression of VIP both in breeding adults, which exhibit morph differences in territorial aggression, and in nestlings, before territorial behavior develops. We extracted and bisulfite-converted DNA from samples of the hypothalamus in wild-caught adults and nestlings and used high-throughput sequencing to measure DNA methylation of a region upstream of the VIP start site. We found that the allele inside the supergene was less methylated than the alternative allele in both adults and nestlings. The differential methylation was attributed primarily to CpG sites that were shared between the alleles, not to polymorphic sites, which suggests that epigenetic regulation is occurring independently of the genetic differentiation within the supergene. This work represents an initial step toward understanding how epigenetic differentiation inside chromosomal inversions leads to the development of alternative behavioral phenotypes.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"21 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/2a/GBB-21-e12831.PMC9744568.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10678448","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}

引用次数: 2

Sex-specific role of the circadian transcription factor NPAS2 in opioid tolerance, withdrawal and analgesia 昼夜节律转录因子NPAS2在阿片类药物耐受、戒断和镇痛中的性别特异性作用

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2022-08-20 DOI: 10.1111/gbb.12829

Stephanie Puig, Micah A. Shelton, Kelly Barko, Marianne L. Seney, Ryan W. Logan

{"title":"Sex-specific role of the circadian transcription factor NPAS2 in opioid tolerance, withdrawal and analgesia","authors":"Stephanie Puig, Micah A. Shelton, Kelly Barko, Marianne L. Seney, Ryan W. Logan","doi":"10.1111/gbb.12829","DOIUrl":"10.1111/gbb.12829","url":null,"abstract":"Opioids like fentanyl remain the mainstay treatment for chronic pain. Unfortunately, opioid's high dependence liability has led to the current opioid crisis, in part, because of side-effects that develop during long-term use, including analgesic tolerance and physical dependence. Both tolerance and dependence to opioids may lead to escalation of required doses to achieve previous therapeutic efficacy. Additionally, altered sleep and circadian rhythms are common in people on opioid therapy. Opioids impact sleep and circadian rhythms, while disruptions to sleep and circadian rhythms likely mediate the effects of opioids. However, the mechanisms underlying these bidirectional relationships between circadian rhythms and opioids remain largely unknown. The circadian protein, neuronal PAS domain protein 2 (NPAS2), regulates circadian-dependent gene transcription in structure of the central nervous system that modulate opioids and pain. Here, male and female wild-type and NPAS2-deficient (NPAS2−/−) mice were used to investigate the role of NPAS2 in fentanyl analgesia, tolerance, hyperalgesia and physical dependence. Overall, thermal pain thresholds, acute analgesia and tolerance to a fixed dose of fentanyl were largely similar between wild-type and NPAS2−/− mice. However, female NPAS2−/− exhibited augmented analgesic tolerance and significantly more behavioral symptoms of physical dependence to fentanyl. Only male NPAS2−/− mice had increased fentanyl-induced hypersensitivity, when compared with wild-type males. Together, our findings suggest sex-specific effects of NPAS2 signaling in the regulation of fentanyl-induced tolerance, hyperalgesia and dependence.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"21 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9744556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10677956","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}

引用次数: 3

Latrophilin-3 heterozygous versus homozygous mutations in Sprague Dawley rats: Effects on egocentric and allocentric memory and locomotor activity 嗜Latrophilin-3杂合与纯合突变在Sprague Dawley大鼠中的作用:对自我中心和异中心记忆和运动活动的影响

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2022-08-19 DOI: 10.1111/gbb.12817

Samantha L. Regan, Chiho Sugimoto, Hannah E. Dawson, Michael T. Williams, Charles V. Vorhees

{"title":"Latrophilin-3 heterozygous versus homozygous mutations in Sprague Dawley rats: Effects on egocentric and allocentric memory and locomotor activity","authors":"Samantha L. Regan, Chiho Sugimoto, Hannah E. Dawson, Michael T. Williams, Charles V. Vorhees","doi":"10.1111/gbb.12817","DOIUrl":"10.1111/gbb.12817","url":null,"abstract":"Latrophilin-3 (LPHN3) is a brain specific G-protein coupled receptor associated with increased risk of attention deficit hyperactivity disorder (ADHD) and cognitive deficits. CRISPR/Cas9 was used to generate a constitutive knockout (KO) rat of Lphn3 by deleting exon 3, based on human data that LPHN3 variants are associated with some cases of ADHD. Lphn3 KO rats are hyperactive with an attenuated response to ADHD medication and have cognitive deficits. Here, we tested KO, heterozygous (HET), and wildtype (WT) rats to determine if there was a gene-dosage effect. We tested the rats in home-cage activity starting at postnatal day (P)35 and P50, followed by tests of egocentric learning (Cincinnati water maze [CWM]), spatial learning (Morris water maze [MWM]), working memory (radial water maze [RWM]), incidental learning (novel object recognition [NOR]), acoustic startle response (ASR) habituation, tactile startle response (TSR) habituation, prepulse modification of acoustic startle, shuttle-box passive avoidance, conditioned freezing, and a mirror image version of the CWM. KO and HET rats were hyperactive. KO and HET rats had egocentric (CWM) and spatial deficits (MWM), increased startle response, and KO rats showed less conditioned freezing on contextual and cued memory; there were no effects on working memory (RWM) or passive avoidance. The selective gene-dosage effect in Lphn3 HET rats indicates that Lphn3 exhibits dominate expression on functions where it is most abundantly expressed (striatum, hippocampus) but not on behaviors mediated by regions of low expression. The data add further evidence to the impact of this synaptic protein on brain function and behavior.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"21 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2d/3d/GBB-21-e12817.PMC9744505.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9195892","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}

引用次数: 0