title: Double Dissociation of the Roles of Metabotropic Glutamate Receptor 5 and Oxytocin Receptor in Discrete Social Behaviors.
abstract: Social interactions in vertebrates are complex phenomena based on affective and cognitive processes. Multiple brain regions and neurotransmitter systems are involved in the expression of social behaviors, but their individual roles in specific aspects of social interactions are not well understood. Here we investigated how Gq-protein-coupled metabotropic glutamate receptor 5 (mGluR5) and oxytocin receptor (Oxtr) affect social affiliation and social memory. We used conditional genetic approaches in which the genes coding for these receptors were knocked out in the lateral septum by infusion of recombinant adeno-associated viral vectors containing Cre recombinase (AAV-Cre). Social behavior was assessed 2 weeks later using a three-chamber paradigm for sociability and preference for social novelty. Septal deletion of mGluR5 abolished sociability while leaving preference for social novelty intact. In contrast, deletion of Oxtr did not affect sociability but significantly impaired preference for social novelty. Nonsocial behaviors or memories, including novel object recognition or fear conditioning, were not affected by these genetic manipulations. Immunohistochemical analyses of the distribution of mGluR5 and Oxtr revealed non-overlapping localization of these receptors within the lateral septum, suggesting that not only different neurotransmitters but also different neuronal types contribute to sociability versus preference for social novelty. Our findings identify highly specialized roles of lateral septal mGluR5 and Oxtr in the the regulation of discrete social behaviors, and suggest that deficits in social interactions, which accompany many mental illnesses, would benefit from comprehensive treatments targeting different components of social functioning.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Ivana
authors.initials: I
authors.lastname: Mesic
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Yomayra F
authors.initials: YF
authors.lastname: Guzman
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Anita L
authors.initials: AL
authors.lastname: Guedea
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Jovasevic
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Corcoran
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Leaderbrand
authors.affiliation: Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, Miyagi, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nishimori
authors.affiliation: Department of Physiology and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Anis
authors.initials: A
authors.lastname: Contractor
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Jelena
authors.initials: J
authors.lastname: Radulovic
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003213:Conditioning, Psychological; D005239:Fear; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics / Q000378:metabolism*; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism*; D021641:Recognition, Psychology / Q000502:physiology; D012686:Septal Nuclei / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: C578936:Grm5 protein, mouse; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D018045:Receptors, Oxytocin; D049452:Green Fluorescent Proteins
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