15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Absence of M-Ras modulates social behavior in mice

      research-article
      , , ,
      BMC Neuroscience
      BioMed Central
      R-Ras3, Social recognition, VNO, Anxiety, Behavior heatmap

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          The molecular mechanisms that determine social behavior are poorly understood. Pheromones play a critical role in social recognition in most animals, including mice, but how these are converted into behavioral responses is largely unknown. Here, we report that the absence of the small GTPase M-Ras affects social behavior in mice.

          Results

          In their interactions with other males, Mras / males exhibited high levels of territorial aggression and social investigations, and increased fear-related behavior. They also showed increased mating behavior with females. Curiously, increased aggression and mating behaviors were only observed when Mras / males were paired with Mras / partners, but were significantly reduced when paired with wild-type (WT) mice. Since mice use pheromonal cues to identify other individuals, we explored the possibility that pheromone detection may be altered in Mras / mice. Unlike WT mice, Mras / did not show a preference for exploring unfamiliar urinary pheromones or unfamiliar isogenic mice. Although this could indicate that vomeronasal function and/or olfactory learning may be compromised in Mras / mice, these observations were not fully consistent with the differential behavioral responses to WT and Mras / interaction partners by Mras / males. In addition, induction of c- fos upon pheromone exposure or in response to mating was similar in WT and Mras / mice, as was the ex vivo expansion of neural progenitors with EGF. This indicated that acute pheromone detection and processing was likely intact. However, urinary metabolite profiles differed between Mras / and WT males.

          Conclusions

          The changes in behaviors displayed by Mras / mice are likely due to a complex combination of factors that may include an inherent predisposition to increased aggression and sexual behavior, and the production of distinct pheromones that could override the preference for unfamiliar social odors. Olfactory and/or social learning processes may thus be compromised in Mras / mice.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12868-015-0209-8) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references76

          • Record: found
          • Abstract: found
          • Article: not found

          Epigenetic programming by maternal behavior.

          Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Ras in cancer and developmental diseases.

            Somatic, gain-of-function mutations in ras genes were the first specific genetic alterations identified in human cancer about 3 decades ago. Studies during the last quarter century have characterized the Ras proteins as essential components of signaling networks controlling cellular proliferation, differentiation, or survival. The oncogenic mutations of the H-ras, N-ras, or K-ras genes frequently found in human tumors are known to throw off balance the normal outcome of those signaling pathways, thus leading to tumor development. Oncogenic mutations in a number of other upstream or downstream components of Ras signaling pathways (including membrane RTKs or cytosolic kinases) have been detected more recently in association with a variety of cancers. Interestingly, the oncogenic Ras mutations and the mutations in other components of Ras/MAPK signaling pathways appear to be mutually exclusive events in most tumors, indicating that deregulation of Ras-dependent signaling is the essential requirement for tumorigenesis. In contrast to sporadic tumors, separate studies have identified germline mutations in Ras and various other components of Ras signaling pathways that occur in specific association with a number of different familial, developmental syndromes frequently sharing common phenotypic cardiofaciocutaneous features. Finally, even without being a causative force, defective Ras signaling has been cited as a contributing factor to many other human illnesses, including diabetes and immunological and inflammatory disorders. We aim this review at summarizing and updating current knowledge on the contribution of Ras mutations and altered Ras signaling to development of various tumoral and nontumoral pathologies.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males.

              Sexual dimorphisms in the brain underlie behavioral sex differences, but the function of individual sexually dimorphic neuronal populations is poorly understood. Neuronal sexual dimorphisms typically represent quantitative differences in cell number, gene expression, or other features, and it is unknown whether these dimorphisms control sex-typical behavior exclusively in one sex or in both sexes. The progesterone receptor (PR) controls female sexual behavior, and we find many sex differences in number, distribution, or projections of PR-expressing neurons in the adult mouse brain. Using a genetic strategy we developed, we have ablated one such dimorphic PR-expressing neuronal population located in the ventromedial hypothalamus (VMH). Ablation of these neurons in females greatly diminishes sexual receptivity. Strikingly, the corresponding ablation in males reduces mating and aggression. Our findings reveal the functions of a molecularly defined, sexually dimorphic neuronal population in the brain. Moreover, we show that sexually dimorphic neurons can control distinct sex-typical behaviors in both sexes. Copyright © 2013 Elsevier Inc. All rights reserved.
                Bookmark

                Author and article information

                Contributors
                annette@brc.ubc.ca
                bwang@brc.ubc.ca
                mariejasmineleung@gmail.com
                john@brc.ubc.ca
                Journal
                BMC Neurosci
                BMC Neurosci
                BMC Neuroscience
                BioMed Central (London )
                1471-2202
                21 October 2015
                21 October 2015
                2015
                : 16
                : 68
                Affiliations
                The Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver, V6T 1Z3 Canada
                Article
                209
                10.1186/s12868-015-0209-8
                4618870
                26490652
                3296879e-f7a6-4180-9fc6-9f1a89e8641d
                © Ehrhardt et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 March 2015
                : 8 October 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Neurosciences
                r-ras3,social recognition,vno,anxiety,behavior heatmap
                Neurosciences
                r-ras3, social recognition, vno, anxiety, behavior heatmap

                Comments

                Comment on this article