Postpartum Depression and Parenting: Role of mPOA circuits in maternal sensitivity

产后抑郁症和育儿：mPOA 回路在母亲敏感性中的作用

• 批准号: 10726256
• 负责人: Mariana Pereira Arboleya
• 金额: $ 41.82万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-25 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10726256
• 关键词: Affect; Animal Model; Behavior; Behavioral; Brain; Calcium; Canine Adenoviruses; Child; Child Abuse and Neglect; Child Care; Child Health; Child Rearing; Clinical; Cognitive; Coupled; Data; Development; Drug Combinations; Enterobacteria phage P1 Cre recombinase; Exhibits; Exposure to; Fiber; Genetic; Goals; Health; Health Benefit; Human; Impairment; Incidence; Infant; Injections; Intervention; Investigation; Knowledge; Maternal Behavior; Medial; Mental Depression; Methods; Modeling; Modification; Molecular; Monitor; Mothers; Motivation; Neurobiology; Neurons; Pathway interactions; Pattern; Personal Satisfaction; Photometry; Play; Postpartum Depression; Prefrontal Cortex; Preoptic Areas; Public Health; Rattus; Research; Role; Signal Transduction; Structure; Syndrome; Technology; Testing; Ventral Tegmental Area; Viral; Well in self; Woman; Work; adverse outcome; caregiving; child neglect; clinically significant; depression model; depressive symptoms; designer receptors exclusively activated by designer drugs; effective intervention; experimental group; experimental study; flexibility; health of the mother; in vivo monitoring; insight; neural circuit; neurobiological mechanism; neuromechanism; offspring; pre-clinical; response; severe mental illness; success; virus Cre recombinase

Project Summary Maternal behavior that is sensitive to the needs of the offspring is essential for healthy development and emotional wellbeing in humans; yet the neural circuits and neurobiological mechanisms that allow such dynamic coordination are not well understood. Our prior work in rats demonstrates that the medial preoptic area (mPOA), a critical node in the circuitry regulating maternal behavior, plays an essential role in this critical maternal ability (referred to here as maternal sensitivity), allowing mothers to promptly and flexibly adjust caregiving behaviors to resolve the constantly changing needs of their offspring. Postpartum depression is a serious health problem affecting women and their babies worldwide, often with tragic implications for the new mother’s ability to sensitively care for her child. Our overall objective is to provide much-needed mechanistic insight into the neurobiological mechanisms by which maternal sensitivity is compromised by postpartum depression. To achieve this goal, we will use intersectional viral strategies and leverage the many strengths of the Wistar-Kyoto (WKY) animal model of depression for molecular, circuit-level and behavioral analysis. Our previous work demonstrated that WKY mother rats exhibit a syndrome of behavioral deficits relative to control strains that closely model major clinical features of postpartum depression, including disturbances in maternal sensitivity. This proposal builds on our previous findings by examining how mPOA neurons that project to the infralimbic cortex (mPOAàIL, AIM 1) and the ventral tegmental area (mPOAàVTA, AIM 2), contribute to maternal sensitivity. Both structures receive direct input from the mPOA and have long been implicated in cognitive and motivational aspects of goal-directed behaviors, including parenting and depression. The first group of experiments will use combined injections of a Cre-dependent inhibitory (hM4Di) or excitatory (hM3Dq) designer receptors exclusively activated by designer drugs (DREADD) into the mPOA, with a retrograde transducing CAV2-Cre virus into the IL or VTA to assess the functional necessity and sufficiency of these pathways for maternal sensitivity. We will also use GCaMP6s combined with CAV2-Cre to selectively monitor the activity of mPOAàIL and mPOAàVTA neurons while WKY and control mothers interact with offspring with varying needs. Considering the consequences of impaired maternal sensitivity on both mother and child health, it is of major clinical significance to understand the neurobiology contributing to this critical maternal ability. This proposal will generate critical new knowledge on how the brain computes dynamic modifications in need signals to generate sensitive patterns of maternal behavior.

项目总结