围产期应激对母性行为的影响及其心理和中枢（mPFC和VTA）神经机制

良好母性行为对母亲和子代健康发展至关重要，当前对应激影响母性行为研究不足。五羟色胺和催产素参与情绪社会和应激调控并相互影响。我们的研究表明内侧前额叶（mPFC）和腹侧被盖区（VTA）的五羟色胺2A和2C受体调节母性行为。本课题将运用多重技术考察围产期应激影响母性行为的心理机制，以及mPFC和VTA内催产素与五羟色胺2A/2C受体交互调节机制、下丘脑室旁核（PVN）-mPFC/VTA催产素能环路的作用。预期结果：围产期应激通过增加母性焦虑和减弱母性动机和执行功能破坏母性行为；mPFC内催产素与五羟色胺2A受体、VTA内催产素与五羟色胺2A或2C受体在调节母性行为及应激效应上相互拮抗；增强PVN-mPFC/VTA催产素能环路活动可反转应激对母性行为的破坏。本课题将进一步探明调控异常母性行为的心理和神经化学与环路机制，有助于揭示产后精神疾病中母性行为异常的神经机制，为产后精神疾病治疗提供启发。

The normal expression of maternal behavior is not only important for the brain and behavioral development of the young, but also critical for the wellbeing of mothers. Considerable attention has been paid to the effects of peripartum (prepartum and postpartum) stress on the development of offspring, yet only a few studies have investigated the influence that stress has on maternal behavior, per se. Our previous work has demonstrated a critical role of serotonin 5-HT2A and 5-HT2C receptors in the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA) in the mediation of maternal behavior in rats. Given the importance of serotonin in emotion regulation, stress sensitivity, and its known interaction with oxytocin (OXT, another important molecule involved in maternal behavior), the present application is designed to (1) explore the effects of peripartum stress on maternal behavior and the underlying psychological mechanisms; (2) determine how serotonin and oxytocin interacts in mPFC and VTA to impact rat maternal behavior; (3) identify the specific roles of paraventricular nucleus (PVN)-mPFC or PVN-VTA oxytocinergic neural circuits in the disrupted maternal behavior induced by peripartum stress. We will focus on the mPFC, and VTA because they are part of the neural network that controls maternal behavior and stress responses. We will first investigate the effect of peripartum stress on maternal behavior and identify the underlying behavioral mechanisms. Then we will test the neuronal activity of PVN, mPFC and VTA using c-Fos immunohistochemistry, and the amount of oxytocin, 5-HT2A and 5-HT2C receptors using quantitative RT-PCR and Western blotting. Next, we will use various pharmacological to manipulate activities of oxytocin, 5-HT2A and 5-HT2C receptors in the mPFC and VTA and see how they change the peripartum stress effect. Finally, we will use chemogenetic tools to manipulate activities of PVN-mPFC or PVN-VTA oxytocinergic neural circuits and see how they change the peripartum stress effect. Expected outcome will be: (1) chronic peripartum stress will disrupt maternal behavior by increasing maternal anxiety and decreasing maternal motivation and executive function; (2) chronic peripartum stress will decrease neuronal activity in the PVN and the amounts of oxytocin receptors in mPFC and/or VTA; (3) the oxytocin receptor and 5-HT2A/2C receptors antagonize each other in the regulation of maternal behavior and peripartum stress effect; (4) Upregulation of the PVN-mPFC and/or PVN-VTA oxytocinergic activity can reverse the disruption of chronic peripartum stress on maternal behavior. This project is significant and innovative because it investigates a novel mechanism (the interactive mechanisms between OXT and 5-HT2A/2C receptors; PVN-mPFC and PVN-VTA oxytocinergic circuits) involved in abnormal expression of maternal behavior. In so doing, it will help identify the behavioral and neural processes linked to altered maternal behavior and postpartum depression and shed light on developing novel strategies for depression treatment.