Motherhood, Oxytocin and the Medial Prefrontal Cortex

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The postpartum period is accompanied by dramatic clianges in hormones, including increased glucocorticoid and decreased estrogen levels. In virgin rodents, high glucocorticoid and low estrogen levels have been associated with diminished dendritic architecture and fewer dendritic spines, sites of excitatory synapses, in the medial prefrontal cortex (mPFC). This hormonal environment has also been shown to negatively impact behaviors mediated by the mPFC, by impairing cognitive function and enhancing anxiety. Despite the known detrimental effects of high glucocorticoid and low estrogen levels, mothers with this hormonal profile exhibit attenuated anxiety. In addition, research conducted during the K99 phase has shown that dendritic spine density is increased in the mPFC of mother rats and that this effect coincides with improved attention and behavioral flexibility, functions that depend on the mPFC. However, the factors that shield the maternal mPFC from the potentially damaging postpartum hormonal milieu remain unknown. The neuropeptide oxytocin has been shown to buffer stress hormone effects on the brain and behavior and may play a role in protecting mPFC structure and function during motherhood. To investigate this, manipulations of oxytocin receptors, cognitive, anxiety, and maternal behavioral assays and measures of structural plasticity will be employed. The results of these studies will inform us ofthe neural and behavioral alterations associated with motherhood and the role that oxytocin may play in these changes. This work serves as the independent portion of the K99/R00 award and will provide the foundation for a research program focused on elucidating the mechanisms of brain resilience.