dc.contributor.authorShantala Arundathi Hari Dass
dc.date.accessioned2014-06-30T04:56:13Z
dc.date.available2014-06-30T04:56:13Z
dc.date.copyright2014en_US
dc.date.issued2014
dc.identifier.citationShantala Arundathi Hari Dass. (2014). Role of arginine vasopressin in modulating plasticity in defensive behavior. Doctoral thesis, Nanyang Technological University, Singapore.
dc.identifier.urihttp://hdl.handle.net/10356/61632
dc.description.abstractSocial behavior can be viewed as a varying output of an approach-avoidance conflict. For example a potential mate elicits a strong ‘approach’ response and a predator induces the very opposite. Social behavior must be plastic to best adapt to a continuously changing (biotic and abiotic) environment. Different external states are mirrored by changes in levels of circulating sex hormones; presence of a mating opportunity elevates testosterone levels while presence of a stressor depresses it. I hypothesize that the plasticity in social behavior is a function of changes in circulating sex hormones; i.e. testosterone in males. Arginine vasopressin (AVP) is a neuropeptide widely implicated in social behavior. In the extrahypothalamic regions of the brain it is highly sensitive to testosterone. Castration causes a drop in AVP projections in the extrahypothalmic zone, medial amygdala (MEA); a change that can be attributed to an androgen dependent hypermethylation of the AVP promotor. For these reasons extrahypothalmic AVP was selected as a candidate target. I focused my studies on the MEA, a part of the social behavior network, which has a central role in social behaviors such as reproductive and defensive behavior. The infection of rats by Toxoplasma gondii is a well suited system to study social behavior. Infected male rats display an attraction to their feline predators. This is a shift of the approach-avoidance conflict from avoidance to approach. I show that this change can be generalized to sexual aspects of the social behavior, coupled with a corresponding increase in testosterone levels. The changes in behavior were apparent in a long-time frame rather than being transient, implying a long lasting robust proximate mechanism. This suggested epigenetic regulation as an ideal candidate. AVP promoter contains two androgen sensitive methylation sites. Infection decreased methylation at both these sites in a sub-nucleus of the MEA. Global hypomethylation (methionine injection; s.c.) in infected males was sufficient to reverse Toxoplasma gondii infection induced behavior changes. Post methionine treatment infected males were no longer attracted to cat odor. Furthermore, hypomethylation by treatment with a DNA methyl transferase inhibitor (RG108) in MEA decreased fear response towards cat odor. I demonstrate that testosterone is necessary to drive the infection induced changes in behavior; localized supplementation of testosterone in the MEA of castrates reduces their fear response. Further an overexpression of AVP in the MEA is sufficient to cause a reduction in the fear response. Based on these findings I propose a model for plasticity of social behavior wherein changes in external environment are mirrored by changes in testosterone levels in males. This in turn changes levels of AVP in the MEA via androgen dependent methylation sites. Decreased methylation of the AVP promoter regions corresponds to increased AVP expression and an ‘approach’ bias in social behavior and vice versa. Taken together these posit a central role for epigenetic modulation of AVP in the MEA as a mediator of plasticity in social behavior. In culmination I propose that social behavior is collectively governed by a trinodal ‘extended social behavior network’. This consists of reciprocally connected nodes; the environment, gonadal milieu and neural circuits.en_US
dc.format.extent192 p.en_US
dc.language.isoenen_US
dc.subjectDRNTU::Scienceen_US
dc.titleRole of arginine vasopressin in modulating plasticity in defensive behavioren_US
dc.typeThesis
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.description.degreeDOCTOR OF PHILOSOPHY (SBS)en_US
dc.contributor.supervisor2Ajai Vyas (SBS)en_US


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