Role of Lateral Septum in Emotional Reactivity During the Postpartum Period

侧隔膜在产后情绪反应中的作用

• 批准号: 7780696
• 负责人: Stephen Coull Gammie
• 金额: $ 33.02万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7780696
• 关键词: Accounting; Adrenergic Agents; Affect; Aggressive behavior; Anxiety; Area; Behavior Disorders; Behavioral; Biological; Brain region; Cessation of life; Child; Clinical; Data; Disease; Emotional; Emotional disorder; Environment; Female; Future; GABA-A Receptor; Gap Junctions; Gene Expression; Goals; Health; Health Personnel; Human; Incidence; Individual; Injection of therapeutic agent; Injury; Intervention; Knowledge; Label; Laboratories; Lactation; Lateral; Lead; Light; Link; Mammals; Mental Depression; Mental Health; Mental disorders; Methods; Mission; Modeling; Mood Disorders; Moods; Mothers; Mus; Neurobiology; Neurons; Neurosciences Research; Outcome; Output; Parents; Pathway interactions; Population; Postpartum Period; Process; Production; Receptor Signaling; Regulation; Research; Research Personnel; Resource Sharing; Resources; Role; Schizophrenia; Signal Transduction; Site; Techniques; Testing; Time; Translational Research; Trauma; Universities; Violence; Western Blotting; Wisconsin; Work; adrenergic; base; beta-adrenergic receptor; cost; endophenotype; experience; gamma-Aminobutyric Acid; innovation; insight; maternal aggression; motherhood; neurochemistry; neuronal circuitry; offspring; psychologic; public health relevance; receptor; relating to nervous system

DESCRIPTION (provided by applicant): Maternal aggression (protection of offspring) provides a nexus for understanding two important mental health issues: emotional changes that occur during the postpartum period and fierce reactive aggression. Maternal aggression (also called maternal defense) is a powerful form of reactive aggression that is produced in the defense of offspring and is highly conserved in mammals ranging from humans to mice. Our long-term goal is to understand the functional neuronal circuitry of maternal aggression. The objective of this application is to determine how beta adrenergic and GABA A receptor signaling in lateral septum (LS) act to regulate maternal aggression. The central hypothesis of the application is that lowering of beta adrenergic receptor signaling in LS is a key step for elevating maternal aggression, while lowering GABA A receptor signaling in LS is a key step in reducing aggressive output. LS contains a large number of GABA-positive neurons, many of which project outside of LS, and we propose that these GABA-positive projection neurons contain and are regulated by beta adrenergic and GABA A receptors in LS. The rationale for the proposed research is that once the mechanisms by which beta adrenergic and GABA A receptors regulate maternal aggression in LS are known, we will gain important insights into neuronal changes during lactation that shed light on postpartum mood disorders. We will also gain information on the basis of fierce reactive aggressive outburst in humans that is expected to provide insights into new interventions. Consequently, the proposed research is relevant to NIH's mission to reduce the burden of mental illness and behavioral disorders. Guided by strong preliminary data, the hypothesis will be tested by pursuing two specific aims: 1) Identify the key receptors that act in LS to regulate maternal aggression; and 2) Identify the neuronal population in LS that is regulated by beta adrenergic and GABA A receptors. Under the first aim, site-specific injection approaches will be used to modulate beta adrenergic and GABA A receptor activity and test effects on maternal aggression. Established Western blotting and real-time PCR techniques will be used to determine the extent to which these receptors show altered expression in association with changes in aggression. Under the second aim, gene expression approaches will be used to identify changes in GABA synthesis that occur in LS in association with changes in aggression. Double/triple labeling approaches along with anterograde and retrograde tracing will be used to determine the extent to which GABA-positive neurons in LS contain GABA A and beta adrenergic receptors and to identify the downstream brain regions that are targets of the GABA-positive projection neurons in LS. The proposed work is innovative because it combines an array of behavioral, pharmacologic, neurobiological, and neurochemical methods to examine an important, but understudied area of maternal aggression. The proposed research is significant, because it will provide critical missing information on how fierce reactive aggression is produced and provide insights into mood changes during the postpartum period. PUBLIC HEALTH RELEVANCE: The proposed studies are on maternal aggression, an important and under-investigated area that has potential applicability to understanding two mental health issues. One benefit of this research is that it is expected to provide insights into neurobiological and emotional changes that occur within the postpartum period and promote new ideas for treatments of postpartum mood disorders. Another benefit of this research is that it is expected to provide insights into the production of maladaptive fierce reactive aggression and open avenues for developing interventions to reduce aggression in humans.

描述（由申请人提供）：母亲的攻击性（保护后代）为理解两个重要的心理健康问题提供了联系：产后期发生的情绪变化和激烈的反应性攻击性。母性攻击（也称为母性防御）是一种强大的反应性攻击形式，在保护后代时产生，并且在从人类到小鼠的哺乳动物中高度保守。我们的长期目标是了解母亲攻击性的功能神经回路。本应用的目的是确定侧隔膜 (LS) 中的 β 肾上腺素能和 GABA A 受体信号传导如何调节母体攻击性。该申请的中心假设是，降低 LS 中的 β 肾上腺素受体信号传导是提高母体攻击性的关键步骤，而降低 LS 中的 GABA A 受体信号传导是减少攻击性输出的关键步骤。 LS 包含大量 GABA 阳性神经元，其中许多投射到 LS 之外，我们提出这些 GABA 阳性投射神经元包含 LS 中的 β 肾上腺素能受体和 GABA A 受体，并受其调节。这项研究的基本原理是，一旦了解 LS 中 β 肾上腺素能和 GABA A 受体调节母体攻击性的机制，我们将获得对哺乳期间神经元变化的重要见解，从而揭示产后情绪障碍。我们还将获得有关人类激烈的反应性攻击爆发的信息，这有望为新的干预措施提供见解。因此，拟议的研究与 NIH 减轻精神疾病和行为障碍负担的使命相关。在强有力的初步数据的指导下，该假设将通过追求两个具体目标进行检验：1）识别在 LS 中发挥作用以调节母性攻击性的关键受体； 2) 鉴定 LS 中受 β 肾上腺素能受体和 GABA A 受体调节的神经元群。在第一个目标下，将使用定点注射方法来调节 β 肾上腺素能和 GABA A 受体活性并测试对母体攻击性的影响。已建立的蛋白质印迹和实时 PCR 技术将用于确定这些受体表现出与攻击性变化相关的表达改变的程度。在第二个目标下，基因表达方法将用于识别 LS 中与攻击性变化相关的 GABA 合成变化。双/三标记方法以及顺行和逆行追踪将用于确定 LS 中 GABA 阳性神经元含有 GABA A 和 β 肾上腺素受体的程度，并确定作为 GABA 阳性投射神经元目标的下游大脑区域在LS。这项工作具有创新性，因为它结合了一系列行为、药理学、神经生物学和神经化学方法来检查母性攻击性这一重要但尚未得到充分研究的领域。拟议的研究意义重大，因为它将提供关于如何产生激烈的反应性攻击的关键缺失信息，并提供对产后情绪变化的见解。 公共卫生相关性：拟议的研究是关于母亲攻击性的，这是一个重要且研究不足的领域，有可能适用于理解两个心理健康问题。这项研究的一个好处是，它有望提供对产后期间发生的神经生物学和情绪变化的见解，并促进产后情绪障碍治疗的新思路。这项研究的另一个好处是，它有望深入了解适应不良的激烈反应性攻击行为的产生，并为开发减少人类攻击行为的干预措施开辟途径。