Abstract
Interactions with others are a fundamental aspect of mammalian life. While multiple biological processes underpin normal mammalian behaviors, oxytocin is a well-studied neuropeptide hormone notable for its role in modulating neural pathways and influencing behavior. Acting within both the viscera and central nervous system, oxytocin regulates a variety of physiological and behavioral functions. Centrally, the oxytocinergic system modulates social behaviors such as bonding, aggression, and complex cognitive functions like empathy. Prairie voles (Microtus ochrogaster), known for their unique social behaviors resembling those of humans, provide an excellent model for studying these processes due to their biparental and socially monogamous nature, which is heavily influenced by the oxytocinergic system.
This dissertation investigates the neuroanatomical circuitry of the prairie vole, focusing on three specific oxytocin systems. In Chapter 1, I review oxytocin’s roles as a hormone in the viscera, a neuropeptide in central regions containing oxytocin axons, and a paracrine molecule in regions with oxytocin dendrites. I discuss how these systems may independently regulate specific behaviors through subcortical circuitry or cortical signaling. I also address a critical question in the field: how does oxytocin exert its effects in the cerebral cortex despite the apparent scarcity of oxytocin axons in this region?
Chapter 2 details the design and development of The Histochemical Brain Atlas of the Prairie Vole. Previous research on prairie voles has relied on brain atlases of other rodents, such as mice and rats. To address this gap, we created a comprehensive histochemical atlas specific to the prairie vole brain, providing a valuable resource for future studies and supporting the aims of Chapter 3.
In Chapter 3, I explore the oxytocinergic system in the prairie vole brain. Using immunohistochemistry, RNAScope in-situ hybridization, and advanced microscopy techniques (electron, confocal, and light sheet), I map the distribution of oxytocin cells and axons across the whole brain and correlate these with the expression of oxytocin receptor transcripts. My findings reveal a lack of correlation between oxytocin axons and Oxtr expression, particularly in the cerebral cortex, where few oxytocin axons coincide with numerous Oxtr-expressing cells. Electron microscopy studies indicate that dendrites of the paraventricular nucleus extend into the third ventricle, releasing oxytocin directly into the cerebrospinal fluid (CSF). This suggests that oxytocin in the CSF travels to the cerebral cortex to bind to oxytocin receptors.
This dissertation elucidates the intricate roles of oxytocin within the prairie vole brain, highlighting the diverse mechanisms by which oxytocin influences social behaviors through its action in different neuroanatomical regions. The development of the prairie vole brain atlas provides a critical tool for future research, facilitating more precise investigations into the neurochemical bases of behavior. The discovery of oxytocin’s diffusion into the cerebrospinal fluid and its subsequent action in the cerebral cortex offers novel insights into oxytocinergic modulation of higher-order cognitive functions.
