Natural Variations within the Oxytocin Receptor Gene Modulate Neural Network Activity Associated with Pair Bonding Behavior in Male Prairie Voles Pubblico
Haddad, Fuad Christopher (2016)
Abstract
BACKGROUND: Oxytocin (OT), a hormonal peptide, has been evolutionarily conserved across a variety of species to regulate reproductive and social behavior. OT acts by binding to oxytocin receptors (OTR) which have been suggested to play a critical role in mating, pair bonding, and maternal behavior. Furthermore, natural OTR variations influence pair bonding behavior. While OTR has been found to modulate functional connectivity across a hypothesized neural network of pair bonding nuclei, the question as to whether naturally occurring variations in OTR expression are associated with differences in functional connectivity remains unclear. Understanding the relationships between natural Oxtr variation (the gene encoding oxytocin receptor) and differences in neural activity during social contexts will provide insights for human social cognition and therapeutic applications for social deficits in autism, depression, schizophrenia, and psychopathy.
METHODS: The prairie vole was used as an experimental model due to its well-researched application as a translational model for pair bonding. Male prairie voles were subjected to a 30 minute cohabitation paradigm with treatment being exposure to a female. Fos, an early immediate gene protein product, was used to quantify neuronal activation and correlated activity within regions of interest (ROIs) associated with pair bonding. Males were genotyped at a previously identified single nucleotide polymorphism within Oxtr to predict levels of central OTR expression.
RESULTS: Analysis of Fos expression demonstrated that natural OTR variation within the nucleus accumbens (NAc) modulates functional connectivity between hypothesized ROIs such that males carrying the high expressing Oxtr genotype displayed decreased correlated activity between the ventral pallidum (VP) and prefrontal cortex (PFC) and anterior olfactory nucleus compared to those with the low expressing Oxtr genotype.
CONCLUSION: Natural variations in OTR lead to modulations in functional connectivity between pair bonding brain nuclei in male prairie voles during sociosexual interaction with a female and provide important insights for understanding how natural OTR variation may affect pair bonding and other complex social behavior.
Table of Contents
Abstract. 1
Introduction. 2
Materials and Methods. 9
Statistical Analysis. 14
Results. 15
Discussion. 16
Conclusion. 21
Appendix A. 22
Figure 1: Partner Preference Test
Figure 2: Hypothetical neuronal model for pair bond formation in prairie voles
Figure 3: Sagittal view of hypothesized pair bonding network in prairie voles
Figure 4: A comparison between oxytocin and vasopressin receptor density between the prairie and montane vole and its consequence on pair bonding behavior
Figure 5: NT213739 genotype is a strong predictor of nucleus accumbens oxytocin receptor density in prairie voles
Figure 6: Hypothesis for NT213739 genotype's effect on hypothesized pair bonding nuclei
Appendix B. 28
Figure 7: Cohabitation and perfusion protocol
Figure 8: Gel electrophoresis after oxytocin receptor gene is processed with BsiHKAI
Figure 9: An anatomical representation of regions of interest and Fos expression
Appendix C. 30
Table 1: Male prairie vole groups comparing treatment (unexposed vs. exposed to female) and mated (mated or did not mate with female) to NT213739 genotype
Table 2: Exposure and mating with a female increases Fos expression in each region of interest
Table 3: Mating does not affect Fos expression in exposed animals per region of interest
Table 4: For mated animals, mean Fos expression does not differ between genotypes in each region of interest
Table 5: Fisher's z to r transformation shows significant interactions between the ventral pallidum and prefrontal cortex
Figure 10: Increases in Fos expression are associated with exposure to female in male prairie voles within regions of interest
Figure 11: Fos covariance heat map for mated low expression (T/T) subjects
Figure 12: Fos covariance heat map for mated NT213739 heterozygous (C/T) subjects
Figure 13: Fos covariance heat map for mated high expression (C/C) subjects
Figure 14: Comparison of prefrontal cortex and ventral pallidum Fos covariance between high (C/C) and low (T/T) expressing oxytocin receptor density mated groups
Figure 15: Revised hypothesis for how NT213739 genotype modulates sociosexual behavior
References. 38
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