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101. Development of a triazolobenzodiazepine-based PET probe for subtype-selective vasopressin 1A receptor imaging

Author

Haider, Ahmed, primary, Xiao, Zhiwei, additional, Xia, Xiaotian, additional, Chen, Jiahui, additional, Van, Richard S., additional, Kuang, Shi, additional, Zhao, Chunyu, additional, Rong, Jian, additional, Shao, Tuo, additional, Ramesh, Perla, additional, Aravind, Appu, additional, Shao, Yihan, additional, Ran, Chongzhao, additional, Young, Larry J., additional, and Liang, Steven H., additional

Published
2021
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113. Additional file 10 of Comparative neurotranscriptomics reveal widespread species differences associated with bonding

Author

Tripp, Joel A., Berrio, Alejandro, McGraw, Lisa A., Matz, Mikhail V., Davis, Jamie K., Inoue, Kiyoshi, Thomas, James W., Young, Larry J., and Phelps, Steven M.

Abstract

Additional file 10: Supplementary Fig. 1. Expression pattern of significant genes is consistent across regions. Plots show counts for samples collected at each pre-mating (0 h) and post-mating (0.5, 2, or 12 h) collection point. Each point represents one sample. Darker shades and triangles represent prairie vole samples. Lighter shades and circles represent meadow vole samples. a. Nfkbia in AMY (above) and VP/NAc (below). b. Pxn in HT (above) and VP/NAc (below). c. Per1 in HT (above) and VP/NAc (below). d. Cables1 in HT (above) and VP/NAc (below). Supplementary Fig. 2. Gene ontology analysis for amygdala gene-expression modules. Enriched GO terms in a. prairie vole green module and b. meadow vole darkorchid module. Hierarchical clustering tree shows relationship between GO categories based on shared genes. Branches with length of zero are subsets of one another. Fractions preceding GO terms indicate proportion of genes from the category that are included in the module of interest. FDR determined by 100 permutations where significance measures are randomly shuffled among genes. Bold text indicates adjusted p

Published
2021
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115. The prairie vole: an emerging model organism for understanding the social brain

Author

McGraw, Lisa A. and Young, Larry J.

Subjects
Brain -- Social aspects, Neurosciences -- Social aspects, Animal behavior -- Social aspects, Health, Psychology and mental health
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tins.2009.11.006 Byline: Lisa A. McGraw (1), Larry J. Young (1)(2) Abstract: Unlike most mammalian species, the prairie vole is highly affiliative, forms enduring social bonds between mates and displays biparental behavior. Over two decades of research on this species has enhanced our understanding of the neurobiological basis not only of monogamy, social attachment and nurturing behaviors but also other aspects of social cognition. Because social cognitive deficits are hallmarks of many psychiatric disorders, discoveries made in prairie voles can direct novel treatment strategies for disorders such as autism spectrum disorder and schizophrenia. With the ongoing development of molecular, genetic and genomic tools for this species, prairie voles will likely maintain their current trajectory becoming an unprecedented model organism for basic and translational research focusing on the biology of the social brain. Author Affiliation: (1) Center for Behavioral Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA (2) Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA

Published
2010

120. Oxytocin Influences Male Sexual Activity via Non-synaptic Axonal Release in the Spinal Cord

Author

Oti, Takumi, Satoh, Keita, Uta, Daisuke, Nagafuchi, Junta, Tateishi, Sayaka, Ueda, Ryota, Takanami, Keiko, Young, Larry J., Galione, Antony, Morris, John F., Sakamoto, Tatsuya, Sakamoto, Hirotaka, Oti, Takumi, Satoh, Keita, Uta, Daisuke, Nagafuchi, Junta, Tateishi, Sayaka, Ueda, Ryota, Takanami, Keiko, Young, Larry J., Galione, Antony, Morris, John F., Sakamoto, Tatsuya, and Sakamoto, Hirotaka

Abstract

Oxytocinergic neurons in the paraventricular nucleus of the hypothalamus that project to extrahypothalamic brain areas and the lumbar spinal cord play an important role in the control of erectile function and male sexual behavior in mammals. The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord is an important component of the neural circuits that control penile reflexes in rats, circuits that are commonly referred to as the “spinal ejaculation generator (SEG).” We have examined the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system in rats. Here, we show that SEG/GRP neurons express oxytocin receptors and are activated by oxytocin during male sexual behavior. Intrathecal injection of oxytocin receptor antagonist not only attenuates ejaculation but also affects pre-ejaculatory behavior during normal sexual activity. Electron microscopy of potassium-stimulated acute slices of the lumbar cord showed that oxytocin-neurophysin-immunoreactivity was detected in large numbers of neurosecretory dense-cored vesicles, many of which are located close to the plasmalemma of axonal varicosities in which no electron-lucent microvesicles or synaptic membrane thickenings were visible. These results suggested that, in rats, release of oxytocin in the lumbar spinal cord is not limited to conventional synapses but occurs by exocytosis of the dense-cored vesicles from axonal varicosities and acts by diffusion—a localized volume transmission—to reach oxytocin receptors on GRP neurons and facilitate male sexual function.

Published
2020

121. AVPR1A variation is linked to gray matter covariation in the social brain network of chimpanzees

Author

Mulholland, Michele M., Navabpour, Shaghayegh V., Mareno, Mary C., Schapiro, Steven J., Young, Larry J., Hopkins, William D., Mulholland, Michele M., Navabpour, Shaghayegh V., Mareno, Mary C., Schapiro, Steven J., Young, Larry J., and Hopkins, William D.

Abstract

The vasopressin system has been implicated in the regulation of social behavior and cognition in humans, nonhuman primates and other social mammals. In chimpanzees, polymorphisms in the vasopressin V1a receptor gene (AVPR1A) have been associated with social dimensions of personality, as well as to responses to sociocommunicative cues and mirror self-recognition. Despite evidence of this association with social cognition and behavior, there is little research on the neuroanatomical correlates of AVPR1A variation. In the current study, we tested the association between AVPR1A polymorphisms in the RS3 promotor region and gray matter covariation in chimpanzees using magnetic resonance imaging and source-based morphometry. The analysis identified 13 independent brain components, three of which differed significantly in covariation between the two AVPR1A genotypes (DupB−/− and DupB+/−; P <.05). DupB+/− chimpanzees showed greater covariation in gray matter in the premotor and prefrontal cortex, basal forebrain, lunate and cingulate cortex, and lesser gray matter covariation in the superior temporal sulcus and postcentral sulcus. Some of these regions were previously found to differ in vasopressin and oxytocin neural fibers between nonhuman primates, and in AVPR1A gene expression in humans with different RS3 alleles. This is the first report of an association between AVPR1A and gray matter covariation in nonhuman primates, and specifically links an AVPR1A polymorphism to structural variation in the social brain network. These results further affirm the value of chimpanzees as a model species for investigating the relationship between genetic variation, brain structure and social cognition with relevance to psychiatric disorders, including autism.

Published
2020

124. Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models

Author

Kandasamy, Lenin C, primary, Tsukamoto, Mina, additional, Banov, Vitaliy, additional, Tsetsegee, Sambuu, additional, Nagasawa, Yutaro, additional, Kato, Mitsuhiro, additional, Matsumoto, Naomichi, additional, Takeda, Junji, additional, Itohara, Shigeyoshi, additional, Ogawa, Sonoko, additional, Young, Larry J, additional, and Zhang, Qi, additional

Published
2021
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125. Effects of Oxytocin on Emotion Recognition in Schizophrenia

Author

Andari, Elissar, primary, Massa, Nicholas M., additional, Fargotstein, Molly D., additional, Taylor, Nicholas B., additional, Halverson, David M., additional, Owens, Andrew V., additional, Currin, Danielle L., additional, Bhattacharya, Arpita, additional, Gitman, Dmitriy, additional, Cuthbert, Bruce C., additional, Young, Larry J., additional, and Duncan, Erica J., additional

Published
2021
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129. Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice

Author

Takayanagi, Yuki, Yoshida, Masahide, Bielsky, Isadora F., Ross, Heather E., Kawamata, Masaki, Onaka, Tatsushi, Yanagisawa, Teruyuki, Kimura, Tadashi, Matzuk, Martin M., Young, Larry J., and Nishimori, Katsuhiko

Subjects
Oxytocin -- Research, Reproduction -- Research, Germ cells -- Research, Science and technology
Abstract

The oxytocin receptor (OXTR) and its ligand, oxytocin (OXT), regulate reproductive physiology (i.e., parturition and lactation) and sociosexual behaviors. To define the essential functions of OXTR, we generated mice with a null mutation in the Oxtr gene ([Oxtr.sup.-/-]) and compared them with OXT-deficient ([Oxt.sup.-/-]) mice. [Oxtr.sup.-/-] mice were viable and had no obvious deficits in fertility or reproductive behavior. [Oxtr.sup.-/-] dams exhibited normal parturition but demonstrated defects in lactation and maternal nurturing. Infant [Oxtr.sup.-/-] males emitted fewer ultrasonic vocalizations than wild-type littermates in response to social isolation. Adult [Oxtr.sup.-/-] males also showed deficits in social discrimination and elevated aggressive behavior. Ligand [Oxt.sup.-/-] males from [Oxt.sup.-/-] dams, but not from [Oxt.sup.+/-] dams, showed similar high levels of aggression. These data suggest a developmental role for the OXT/OXTR system in shaping adult aggressive behavior. Our studies demonstrate that OXTR plays a critical role in regulating several aspects of social behavior and may have important implications for developmental psychiatric disorders characterized by deficits in social behavior. lactation | maternal behavior | ultrasonic vocalization | social discrimination | aggressive behavior

Published
2005

132. Microsatellite instability generates diversity in brain and sociobehavioral traits

Author

Hammock, Elizabeth A.D. and Young, Larry J.

Subjects
Brain -- Research, Social sciences -- Research, Science and technology
Abstract

Repetitive microsatellites mutate at relatively high rates and may contribute to the rapid evolution of species-typical traits. We show that individual alleles of a repetitive polymorphic microsateUite in the 5' region of the prairie vole vasopressin 1a receptor (avpr1a) gene modify gene expression in vitro. In vivo, we observe that this regulatory polymorphism predicts both individual differences in receptor distribution patterns and socio-behavioral traits. These data suggest that individual differences in gene expression patterns may be conferred via polymorphic microsatellites in the cis-regulatory regions of genes and may contribute to normal variation in behavioral traits., Social behavior evolves rapidly as evidenced by the diversity of species-typical social structures among closely related species; however, the underlying mechanisms of this rapid evolution are currently unknown. Evolution of [...]

Published
2005

133. Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene

Author

Lim, Miranda M., Wang, Zuoxin, Olazabal, Daniel E., Ren, Xianghui, Terwilliger, Ernest F., and Young, Larry J.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Miranda M. Lim [1]; Zuoxin Wang [2]; Daniel E. Olazábal [1]; Xianghui Ren [3]; Ernest F. Terwilliger [3]; Larry J. Young (corresponding author) [1] The molecular mechanisms underlying the [...]

Published
2004
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140. Mutation of a novel gene results in abnormal development of spermatid flagella, loss of intermale aggression and reduced body fat in mice

Author

Campbell, Patrick K., Waymire, Katrina G., Heier, Robb L., Sharer, Catherine, Day, Diane E., Reiman, Heike, Jaje, J. Michael, Friedrich, Glenn A., Burmeister, Margit, Bartness, Timothy J., Russell, Lonnie D., Young, Larry J., Zimmer, Michael, Jenne, Dieter E., and MacGregor, Grant R.

Subjects
Genetics -- Research, Gene mutations -- Physiological aspects, Flagella (Microbiology) -- Genetic aspects, Spermatogenesis -- Research, Courtship of animals -- Research, Testosterone -- Genetic aspects, Biological sciences
Abstract

ROSA22 male mice are sterile due to a recessive gene-trap mutation that affects development of the spermatid flagellum. The defect involves the flagellar axoneme, which becomes unstable around the time of its assembly. Despite a subsequent complete failure in flagellar assembly, development of the spermatid head appears normal and the spermatid head is released at the correct stage in spermatogenesis. The mutation is pleiotropic. Although ROSA22 homozygote males have normal levels of circulating testosterone and display normal mating behavior, they do not exhibit intermale aggressive behavior and have reduced body fat. The mutated gene (Gtrgeo22) maps to mouse chromosome 10 and is closely flanked by two known genes, Madcam1 and Cdc34. Ribonuclease protection analysis indicates that expression of the flanking genes is unaffected by the mutation. Gtrgeo22 is expressed at low levels in epithelial cells in several tissues, as well as in testis and brain. Analysis of the peptide coding sequence suggests that Gtrgeo22 encodes a novel transmembrane protein, which contains dileucine and tyrosine-based motifs involved in intracellular sorting of transmembrane proteins. Analysis of the Gtrgeo22 gene product should provide novel insight into the molecular basis for intermale aggression and sperm flagellar development.

Published
2002

144. List of Contributors

Author

Acri, Jane B., primary, Borsini, Franco, additional, Bergman, Jack, additional, Chiamulera, Christian, additional, Comer, Sandra, additional, Dourish, Colin T., additional, Gardner, Tracie J., additional, Grant, Jon E., additional, Halford, Jason, additional, Haney, Margaret, additional, Heidbreder, Christian A., additional, Koob, George F., additional, Kosten, Therese, additional, Kosten, Thomas, additional, Little, Hilary J., additional, Markou, Athina, additional, McArthur, Robert A., additional, McCann, David J., additional, McKinzie, David L., additional, Potenza, Marc N., additional, Rocha, Beatriz A., additional, Sellers, Edward M., additional, Setnik, Beatrice, additional, Shram, Megan J., additional, Spealman, Roger D., additional, Vocci, Frank, additional, West, Robert J., additional, Wilding, John P.H., additional, Williams, Wendol A., additional, Winstanley, Catharine A., additional, Willner, Paul, additional, Bartz, Jennifer A., additional, Brady, Linda, additional, Buxbaum, Joseph D., additional, Campbell, Brian, additional, Chappell, Phillip, additional, Cryan, John F., additional, Dinan, Timothy G., additional, Doran, Scott M., additional, Driscoll, Jamie, additional, Einat, Haim, additional, Freudenreich, Oliver, additional, Gartlon, Jane E., additional, Geyer, Mark A., additional, Hollander, Eric, additional, Holmes, Andrew, additional, Joel, Daphna, additional, Jones, Declan N.C., additional, Kilduff, Thomas S., additional, Large, Charles H., additional, Mahableshwarkar, Atul R., additional, McEvoy, Joseph P., additional, Miczek, Klaus A., additional, Millan, Mark J., additional, Minassian, Arpi, additional, Ouellet, Daniele, additional, Perry, William, additional, Renger, John J., additional, Ring, Robert H., additional, Sánchez, Connie, additional, Schreiber, Rudy, additional, Seymour, Patricia, additional, Soares, Holly, additional, Steckler, Thomas, additional, Stein, Murray B., additional, Stein, Dan J., additional, Tannock, Rosemary, additional, Turek, Fred, additional, Wang, Paul, additional, Wessel, Thomas, additional, Winsky, Lois, additional, and Young, Larry J., additional

Published
2008
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146. Limb-clasping, cognitive deficit and increased vulnerability to kainic acid - induced seizures in neuronal GPI anchor deficiency mouse models

Author

Kandasamy, Lenin C., primary, Tsukamoto, Mina, additional, Banov, Vitaliy, additional, Tsetsegee, Sambuu, additional, Nagasawa, Yutaro, additional, Kato, Mitsuhiro, additional, Matsumoto, Naomichi, additional, Takeda, Junji, additional, Itohara, Shigeyoshi, additional, Ogawa, Sonoko, additional, Young, Larry J., additional, and Zhang, Qi, additional

Published
2020
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147. Correction: The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure

Author

McLean, Samuel A., primary, Ressler, Kerry, additional, Koenen, Karestan Chase, additional, Neylan, Thomas, additional, Germine, Laura, additional, Jovanovic, Tanja, additional, Clifford, Gari D., additional, Zeng, Donglin, additional, An, Xinming, additional, Linnstaedt, Sarah, additional, Beaudoin, Francesca, additional, House, Stacey, additional, Bollen, Kenneth A., additional, Musey, Paul, additional, Hendry, Phyllis, additional, Jones, Christopher W., additional, Lewandowski, Christopher, additional, Swor, Robert, additional, Datner, Elizabeth, additional, Mohiuddin, Kamran, additional, Stevens, Jennifer S., additional, Storrow, Alan, additional, Kurz, Michael Christopher, additional, McGrath, Meghan E., additional, Fermann, Gregory J., additional, Hudak, Lauren A., additional, Gentile, Nina, additional, Chang, Anna Marie, additional, Peak, David A., additional, Pascual, Jose L., additional, Seamon, Mark J., additional, Sergot, Paulina, additional, Peacock, W. Frank, additional, Diercks, Deborah, additional, Sanchez, Leon D., additional, Rathlev, Niels, additional, Domeier, Robert, additional, Haran, John Patrick, additional, Pearson, Claire, additional, Murty, Vishnu P., additional, Insel, Thomas R., additional, Dagum, Paul, additional, Onnela, Jukka-Pekka, additional, Bruce, Steven E., additional, Gaynes, Bradley N., additional, Joormann, Jutta, additional, Miller, Mark W., additional, Pietrzak, Robert H., additional, Buysse, Daniel J., additional, Pizzagalli, Diego A., additional, Rauch, Scott L., additional, Harte, Steven E., additional, Young, Larry J., additional, Barch, Deanna M., additional, Lebois, Lauren A. M., additional, van Rooij, Sanne J. H., additional, Luna, Beatriz, additional, Smoller, Jordan W., additional, Dougherty, Robert F., additional, Pace, Thaddeus W. W., additional, Binder, Elisabeth, additional, Sheridan, John F., additional, Elliott, James M., additional, Basu, Archana, additional, Fromer, Menachem, additional, Parlikar, Tushar, additional, Zaslavsky, Alan M., additional, and Kessler, Ronald, additional

Published
2020
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