{"title":"Alteration of neural activity and neuroinflammatory factors in the insular cortex of mice with corneal neuropathic pain","authors":"Rui Xu, Yu-Wen Zhang, Qing Gu, Tian-Jie Yuan, Bing-Qian Fan, Jun-Ming Xia, Jin-Hong Wu, Ying Xia, Wen-Xian Li, Yuan Han","doi":"10.1111/gbb.12842","DOIUrl":"10.1111/gbb.12842","url":null,"abstract":"<p>Dry eye disease (DED) affects nearly 55% of people worldwide; several studies have proposed that central sensitization and neuroinflammation may contribute to the developing corneal neuropathic pain of DED, while the underlying mechanisms of this contribution remain to be investigated. Excision of extra orbital lacrimal glands established the dry eye model. Corneal hypersensitivity was examined through chemical and mechanical stimulation, and open field test measured the anxiety levels. Restingstate fMRI is a method of functional magnetic resonance imaging (rs-fMRI) was performed for anatomical involvement of the brain regions. The amplitude of low-frequency fluctuation (ALFF) determined brain activity. Immunofluorescence testing and Quantitative real-time polymerase chain reaction were also performed to further validate the findings. Compared with the Sham group, ALFF signals in the supplemental somatosensory area, secondary auditory cortex, agranular insular cortex, temporal association areas, and ectorhinal cortex brain areas were increased in the dry eye group. This change of ALFF in the insular cortex was linked with the increment in corneal hypersensitivity (<i>p</i> < 0.01), c-Fos (<i>p</i> < 0.001), brain-derived neurotrophic factor (<i>p</i> < 0.01), TNF-α, IL-6, and IL-1β (<i>p</i> < 0.05). In contrast, IL-10 levels (<i>p</i> < 0.05) decreased in the dry eye group. DED-induced corneal hypersensitivity and upregulation of inflammatory cytokines could be blocked by insular cortex injection of Tyrosine Kinase receptor B agonist cyclotraxin-B (<i>p</i> < 0.01) without affecting anxiety levels. Our study reveals that the functional activity of the brain associated with corneal neuropathic pain and neuroinflammation in the insular cortex might contribute to dry eye-related corneal neuropathic pain.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/70/cc/GBB-22-e12842.PMC10067426.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9316970","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 genome-wide association study identified new variants associated with mathematical abilities in Chinese children","authors":"Liming Zhang, Zhengjun Wang, Zijian Zhu, Qing Yang, Chen Cheng, Shunan Zhao, Chunyu Liu, Jingjing Zhao","doi":"10.1111/gbb.12843","DOIUrl":"10.1111/gbb.12843","url":null,"abstract":"<p>Mathematical ability is moderately heritable, and it is a complex trait which can be evaluated in several different categories. A few genetic studies have been published on general mathematical ability. However, no genetic study focused on specific mathematical ability categories. In this study, we separately performed genome-wide association studies on 11 mathematical ability categories in 1146 students from Chinese elementary schools. We identified seven genome-wide significant single nucleotide polymorphisms (SNPs) with strong linkage disequilibrium among each other (all <i>r</i><sup>2</sup> > 0.8) associated with mathematical reasoning ability (top SNP: rs34034296, <i>p</i> = 2.01 × 10<sup>−8</sup>, nearest gene: CUB and Sushi multiple domains 3, CSMD3). We replicated one SNP (rs133885) from 585 SNPs previously reported to be associated with general mathematical ability associated with division ability in our data (<i>p</i> = 1.053 × 10<sup>−5</sup>). In the gene- and gene-set enrichment analysis by MAGMA, we found three significant enrichments of associations with three mathematical ability categories for three genes (LINGO2, OAS1 and HECTD1). We also observed four significant enrichments of associations with four mathematical ability categories for three gene sets. Our results suggest new candidate genetic loci for the genetics of mathematical ability.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/d5/GBB-22-e12843.PMC10067424.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9262505","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}
João Ricardo Sato, Claudinei Eduardo Biazoli, Ana Paula Arantes Bueno, Arthur Caye, Pedro Mario Pan, Marcos Santoro, Jessica Honorato-Mauer, Giovanni Abrahão Salum, Marcelo Queiroz Hoexter, Rodrigo Affonseca Bressan, Andrea Parolin Jackowski, Euripedes Constantino Miguel, Sintia Belangero, Luis Augusto Rohde
{"title":"Polygenic risk score for attention-deficit/hyperactivity disorder and brain functional networks segregation in a community-based sample","authors":"João Ricardo Sato, Claudinei Eduardo Biazoli, Ana Paula Arantes Bueno, Arthur Caye, Pedro Mario Pan, Marcos Santoro, Jessica Honorato-Mauer, Giovanni Abrahão Salum, Marcelo Queiroz Hoexter, Rodrigo Affonseca Bressan, Andrea Parolin Jackowski, Euripedes Constantino Miguel, Sintia Belangero, Luis Augusto Rohde","doi":"10.1111/gbb.12838","DOIUrl":"10.1111/gbb.12838","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Neuroimaging studies suggest that brain development mechanisms might explain at least some behavioural and cognitive attention-deficit/hyperactivity disorder (ADHD) symptoms. However, the putative mechanisms by which genetic susceptibility factors influence clinical features via alterations of brain development remain largely unknown. Here, we set out to integrate genomics and connectomics tools by investigating the associations between an ADHD polygenic risk score (ADHD-PRS) and functional segregation of large-scale brain networks. With this aim, ADHD symptoms score, genetic and rs-fMRI (resting-state functional magnetic resonance image) data obtained in a longitudinal community-based cohort of 227 children and adolescents were analysed. A follow-up was conducted approximately 3 years after the baseline, with rs-fMRI scanning and ADHD likelihood assessment in both stages. We hypothesised a negative correlation between probable ADHD and the segregation of networks involved in executive functions, and a positive correlation with the default-mode network (DMN). Our findings suggest that ADHD-PRS is correlated with ADHD at baseline, but not at follow-up. Despite not surviving for multiple comparison correction, we found significant correlations between ADHD-PRS and segregation of cingulo-opercular networks and DMN at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation. These directions of associations corroborate the proposed counter-balanced role of attentional networks and DMN in attentional processes. However, the association between ADHD-PRS and brain networks functional segregation was not found at follow-up. Our results provide evidence for specific influences of genetic factors on development of attentional networks and DMN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>We found significant correlations between polygenic risk score for ADHD (ADHD-PRS) and segregation of cingulo-opercular networks and default-mode network (DMN) at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/04/GBB-22-e12838.PMC10067387.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9262506","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}
D. Parker Kelley, Lucas Albrechet-Souza, Shealan Cruise, Rajani Maiya, Aspasia Destouni, Siva S. V. P. Sakamuri, Alexander Duplooy, Meghan Hibicke, Charles Nichols, Prasad V. G. Katakam, Nicholas W. Gilpin, Joseph Francis
{"title":"Conditioned place avoidance is associated with a distinct hippocampal phenotype, partly preserved pattern separation, and reduced reactive oxygen species production after stress","authors":"D. Parker Kelley, Lucas Albrechet-Souza, Shealan Cruise, Rajani Maiya, Aspasia Destouni, Siva S. V. P. Sakamuri, Alexander Duplooy, Meghan Hibicke, Charles Nichols, Prasad V. G. Katakam, Nicholas W. Gilpin, Joseph Francis","doi":"10.1111/gbb.12840","DOIUrl":"10.1111/gbb.12840","url":null,"abstract":"<p>Stress is associated with contextual memory deficits, which may mediate avoidance of trauma-associated contexts in posttraumatic stress disorder. These deficits may emerge from impaired pattern separation, the independent representation of similar experiences by the dentate gyrus-Cornu Ammonis 3 (DG-CA3) circuit of the dorsal hippocampus, which allows for appropriate behavioral responses to specific environmental stimuli. Neurogenesis in the DG is controlled by mitochondrial reactive oxygen species (ROS) production, and may contribute to pattern separation. In Experiment 1, we performed RNA sequencing of the dorsal hippocampus 16 days after stress in rats that either develop conditioned place avoidance to a predator urine-associated context (Avoiders), or do not (Non-Avoiders). Weighted genome correlational network analysis showed that increased expression of oxidative phosphorylation-associated gene transcripts and decreased expression of gene transcripts for axon guidance and insulin signaling were associated with avoidance behavior. Based on these data, in Experiment 2, we hypothesized that Avoiders would exhibit elevated hippocampal (HPC) ROS production and degraded object pattern separation (OPS) compared with Nonavoiders. Stress impaired pattern separation performance in Non-Avoider and Avoider rats compared with nonstressed Controls, but surprisingly, Avoiders exhibited partly preserved pattern separation performance and significantly lower ROS production compared with Non-Avoiders. Lower ROS production was associated with better OPS performance in Stressed rats, but ROS production was not associated with OPS performance in Controls. These results suggest a strong negative association between HPC ROS production and pattern separation after stress, and that stress effects on these outcome variables may be associated with avoidance of a stress-paired context.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/57/6b/GBB-22-e12840.PMC10067435.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9256076","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}
Maren L. Smith, Kristin M. Mignogna, Jo L. Rokita, Lorna MacLeod, M. Imad Damaj, Michael F. Miles
{"title":"Identification of candidate genes for nicotine withdrawal in C57BL/6J × DBA/2J recombinant inbred mice","authors":"Maren L. Smith, Kristin M. Mignogna, Jo L. Rokita, Lorna MacLeod, M. Imad Damaj, Michael F. Miles","doi":"10.1111/gbb.12844","DOIUrl":"10.1111/gbb.12844","url":null,"abstract":"<p>Nicotine is the reinforcing ingredient in tobacco. Following chronic exposure, sudden cessation of nicotine use produces negative symptoms of withdrawal that contribute to dependence. The molecular mechanisms underlying nicotine withdrawal behaviors, however, are poorly understood. Using recombinant inbred mice, chronic nicotine was delivered by minipump and withdrawal induced using mecamylamine. Somatic signs of withdrawal, and anxiety-like behavior using elevated plus maze, were then assessed. Interval mapping was used to identify associations between genetic variation and withdrawal behaviors, and with basal gene expression. Differential gene expression following nicotine exposure and withdrawal was also assessed in progenitor mice using microarrays. Quantitative trait loci mapping identified chromosome intervals with significant genetic associations to somatic signs of withdrawal or withdrawal-induced anxiety-like behavior. Using bioinformatics, and association with basal gene expression in nucleus accumbens, we implicated <i>Rb1</i>, <i>Bnip3l</i>, <i>Pnma2</i>, <i>Itm2b</i>, and <i>Kif13b</i> as candidate genes for somatic signs of withdrawal, and <i>Galr1</i>, which showed trans-regulation from a region of chromosome 14 that was associated with somatic signs of withdrawal. Candidate genes within the chromosome 9 region associated with anxiety-like withdrawal behavior included <i>Dixdc1</i>, <i>Ncam1</i>, and <i>Sorl1</i>. Bioinformatics identified six genes that were also significantly associated with nicotine or alcohol traits in recent human genome-wide association studies. Withdrawal-associated somatic signs and anxiety-like behavior had strong non-overlapping genetic associations, respectively, with regions of chromosome 14 and chromosome 9. Genetic, behavioral and gene expression correlations, and bioinformatics analysis identified several candidate genes that may represent novel molecular targets for modulating nicotine withdrawal symptoms.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/ff/GBB-22-e12844.PMC10067406.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9262479","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}
Dorit Möhrle, Megan Yuen, Alice Zheng, Faraj L. Haddad, Brian L. Allman, Susanne Schmid
{"title":"Characterizing maternal isolation-induced ultrasonic vocalizations in a gene–environment interaction rat model for autism","authors":"Dorit Möhrle, Megan Yuen, Alice Zheng, Faraj L. Haddad, Brian L. Allman, Susanne Schmid","doi":"10.1111/gbb.12841","DOIUrl":"10.1111/gbb.12841","url":null,"abstract":"<p>Deficits in social communication and language development belong to the earliest diagnostic criteria of autism spectrum disorders. Of the many risk factors for autism spectrum disorder, the contactin-associated protein-like 2 gene, <i>CNTNAP2</i>, is thought to be important for language development. The present study used a rat model to investigate the potential compounding effects of autism spectrum disorder risk gene mutation and environmental challenges, including breeding conditions or maternal immune activation during pregnancy, on early vocal communication in the offspring. Maternal isolation-induced ultrasonic vocalizations from <i>Cntnap2</i> wildtype and knockout rats at selected postnatal days were analyzed for their acoustic, temporal and syntax characteristics. <i>Cntnap2</i> knockout pups from heterozygous breeding showed normal numbers and largely similar temporal structures of ultrasonic vocalizations to wildtype controls, whereas both parameters were affected in homozygously bred knockouts. Homozygous breeding further exacerbated altered pitch and transitioning between call types found in <i>Cntnap2</i> knockout pups from heterozygous breeding. In contrast, the effect of maternal immune activation on the offspring's vocal communication was confined to call type syntax, but left ultrasonic vocalization acoustic and temporal organization intact. Our results support the “double-hit hypothesis” of autism spectrum disorder risk gene–environment interactions and emphasize that complex features of vocal communication are a useful tool for identifying early autistic-like features in rodent models.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/97/GBB-22-e12841.PMC10242206.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9719465","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}
Dana R. Hodorovich, Patrick M. Lindsley, Austen A. Berry, Derek F. Burton, Kurt C. Marsden
{"title":"Morphological and sensorimotor phenotypes in a zebrafish CHARGE syndrome model are domain-dependent","authors":"Dana R. Hodorovich, Patrick M. Lindsley, Austen A. Berry, Derek F. Burton, Kurt C. Marsden","doi":"10.1111/gbb.12839","DOIUrl":"10.1111/gbb.12839","url":null,"abstract":"<p>CHARGE syndrome is a heterogeneous disorder characterized by a spectrum of defects affecting multiple tissues and behavioral difficulties such as autism, attention-deficit/hyperactivity disorder, obsessive–compulsive disorder, anxiety, and sensory deficits. Most CHARGE cases arise from <i>de novo</i>, loss-of-function mutations in chromodomain-helicase-DNA-binding-protein-7 (CHD7). CHD7 is required for processes such as neuronal differentiation and neural crest cell migration, but how CHD7 affects neural circuit function to regulate behavior is unclear. To investigate the pathophysiology of behavioral symptoms in CHARGE, we established a mutant <i>chd7</i> zebrafish line that recapitulates multiple CHARGE phenotypes including ear, cardiac, and craniofacial defects. Using a panel of behavioral assays, we found that <i>chd7</i> mutants have specific auditory and visual behavior deficits that are independent of defects in sensory structures. Mauthner cell-dependent short-latency acoustic startle responses are normal in <i>chd7</i> mutants, while Mauthner-independent long-latency responses are reduced. Responses to sudden decreases in light are also reduced in mutants, while responses to sudden increases in light are normal, suggesting that the retinal OFF pathway may be affected. Furthermore, by analyzing multiple <i>chd7</i> alleles we observed that the penetrance of morphological and behavioral phenotypes is influenced by genetic background but that it also depends on the mutation location, with a chromodomain mutation causing the highest penetrance. This pattern is consistent with analysis of a CHARGE patient dataset in which symptom penetrance was highest in subjects with mutations in the CHD7 chromodomains. These results provide new insight into the heterogeneity of CHARGE and will inform future work to define CHD7-dependent neurobehavioral mechanisms.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a7/0e/GBB-22-e12839.PMC10242184.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9719449","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}
Cameron R. Love, Sumit Gautam, Chamala Lama, Nhu Hoa Le, Brigitte Dauwalder
{"title":"The Drosophila dopamine 2-like receptor D2R (Dop2R) is required in the blood brain barrier for male courtship","authors":"Cameron R. Love, Sumit Gautam, Chamala Lama, Nhu Hoa Le, Brigitte Dauwalder","doi":"10.1111/gbb.12836","DOIUrl":"10.1111/gbb.12836","url":null,"abstract":"<p>The blood brain barrier (BBB) has the essential function to protect the brain from potentially hazardous molecules while also enabling controlled selective uptake. How these processes and signaling inside BBB cells control neuronal function is an intense area of interest. Signaling in the adult <i>Drosophila</i> BBB is required for normal male courtship behavior and relies on male-specific molecules in the BBB. Here we show that the dopamine receptor <i>D2R</i> is expressed in the BBB and is required in mature males for normal mating behavior. Conditional adult male knockdown of <i>D2R</i> in BBB cells causes courtship defects. The courtship defects observed in genetic <i>D2R</i> mutants can be rescued by expression of normal <i>D2R</i> specifically in the BBB of adult males. <i>Drosophila</i> BBB cells are glial cells. Our findings thus identify a specific glial function for the <i>DR2</i> receptor and dopamine signaling in the regulation of a complex behavior.</p>","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/0b/47/GBB-22-e12836.PMC9994173.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9073393","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}
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":"<p>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.</p>","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}
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":"<p>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 <i>Ndufa13</i>, 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.</p>","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}