Browsing by Subject "Avpr1a"
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Item An analysis of gene expression in the socially monogamous brain(2023-04-24) Ikpatt, Jason Edidiong; Phelps, Steven Michael, 1971-; Xhemalce, Blerta; Iyer, Vishy; Champagne, FrancesSocially monogamous behavior in the prairie vole Microtus ochrogaster is modulated by AVPR1A, a gene that encodes the receptor V1AR. V1AR binds vasopressin released into the brain during mating and helps to facilitate the generation of a pair bond. Notably, V1AR abundance in the nucleus accumbens, ventral pallidum, and retrosplenial area each predict aspects of socially monogamous behavior in the male vole. In my dissertation work, I use fluorescence in-situ hybridization to mark avpr1a expression throughout the vole brain. I imaged sections with fluorescently labelled avpr1a transcript brain-wide and digitally compiled a three-dimensional map of expression patterns of avpr1a transcript in the vole brain, registering them against the Allen Mouse Brain Atlas to uncover a complete list of structures and substructures expressing avpr1a. I categorized this list by both avpr1a-cell density and total avpr1a-cell abundance within a given brain structure. From this digital map, I generated whole-brain models of avpr1a expression patterns in three-dimensional space, visualizing putative social monogamy neural circuitry. I also worked on a project generating transgenic mice to express lacZ under the control of PPEn, a putative pallidal enhancer capable of driving avpr1a expression in the Microtus ochrogaster brain. Here I helped to uncover a list of brain structures where PPEn drives gene expression at different levels. We found that PPEn also suppresses gene expression in the liver, indicative of the important role AVPR1A plays in non-attachment related mammalian bodily functions. Last, I focused on the role of memory in the retrosplenial area in socially monogamous behavior. I used compartmental analysis of transcription Fluorescence In-Situ Hybridization (catFISH) to capture a partner memory engram – a group of cells in the retrosplenial cortex that seem to be involved in the recall of the memory of a mate. I found that mate recall activates a putative engram in the retrosplenial cortex. I discuss how these three analyses of gene expression further our knowledge of the cellular and molecular neurobiology of socially monogamous behavior.Item Molecular regulation of vasopressin receptor among (mostly) monogamous prairie voles(2016-12-16) Okhovat, Mariam; Phelps, Steven Michael, 1970-; Hofmann, Johann A; Vokes, Steven A; Matz, Mikhail; Atkinson, NigelIntraspecific variation in social behavior is common and often dramatic, but little is known about its underlying mechanisms. We use the prairie vole (Microtus ochrogaster) to examine how intraspecific variation in brain and behavior emerges as a result of genetic, epigenetic and environmental variation. Although prairie voles are socially monogamous, they vary in sexual fidelity; faithful prairie voles are described as intra-pair fertilizing (IPF), while unfaithful voles are extra-pair fertilizing (EPF). EPF males have large home-ranges and frequently mate with other females, but do so at the cost of being cuckolded. IPF males however, form small exclusive home-ranges, rarely intrude and are better at mate-guarding. These behavioral differences are predicted by abundance of the vasopressin receptor 1a (V1aR) in the retrosplenial cortex (RSC), a brain region implicated in spatial memory. We find that variation in RSC-V1aR and associated behaviors are predicted by two alternative avpr1a alleles. These “HI” and “LO” alleles are defined by four linked single nucleotide polymorphisms, one of which is a polymorphic CpG site (polyCpG) located within a putative intron enhancer. This polyCpG is weakly linked to several other polyCpGs in the enhancer. Since CpGs are targets for DNA methylation, polyCpGs may cause individual differences in DNA methylation, gene regulation and environmental sensitivity. The unusually high number of polyCpGs within the intron enhancer drives avpr1a genotype differences in CpG density and methylation, which predict avpr1a expression and RSC-V1aR. Examination of avpr1a methylation among wild-caught voles also showed that RSC-V1aR correlated with enhancer methylation, possibly due to genotype differences in enhancer silencing or affinity for transcription factors, but not with promoter methylation. We also found that genotype differences in RSC-V1aR emerge in the first postnatal week, along with changes in enhancer methylation. Before this neurodevelopmental stage, the LO allele, which has more enhancer CpGs, is more sensitive to environmentally-induced changes in RSC-V1aR. These changes however, are not caused by alteration of enhancer methylation, suggesting additional regulatory elements contribute to genotype differences in RSC-V1aR regulation and its environmental sensitivity. Our findings show how genetic and epigenetic variation at a critical gene can shape intraspecific variation in brain and behavior.