Maternal Control Over Developing Prefrontal Cortex and Transition in Independence

母亲对前额皮质发育和独立过渡的控制

基本信息

批准号：
10359146
负责人：
REGINA Marie SULLIVAN
金额：
$ 47.3万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-16 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10359146
关键词：
Adaptive Behaviors Address Adult Age Agonist Amygdaloid structure Anterior Area Attention deficit hyperactivity disorder Avoidance Learning Behavior Behavioral Biological Models Brain Brain region Caregivers Child Child Behavior Complex Data Dependence Development Dopamine Electrophysiology (science)Equation Event Exhibits FOS gene Fright Functional Magnetic Resonance Imaging Functional disorder Growth Health Human Immediate-Early Genes Immunohistochemistry Individual Infant Learning Lesion Life Measures Mental Depression Modeling Mothers Neonatal Odors Organism Pain Pathology Pathway interactions Pattern Prefrontal Cortex Preparation Rattus Research Role Shock Signal Transduction Source Stimulus Structure System Techniques Testing Translational Research Translations Ventral Tegmental Area Weaning analytical tool antagonist base cingulate cortex conditioned fear conditioning developmental disease flexibility juvenile animal learning ability neonate neural circuit neurobehavioral novel novel strategies preference public health relevance pup receptor relating to nervous system response

项目摘要

DESCRIPTION (provided by applicant): Development is a period of neurobehavioral changes requiring immature organisms to exhibit behavioral flexibility to adapt to the world. A traditional view of development sees existing brain circuits becoming more complex to accommodate behavioral change. While certainly sometimes true, additional research suggests that developing organisms must sometimes change the neural circuitry evoked by a specific event for expression of the more mature behavior. For example, as infants transition from dependence on the mother to independence, at least some new neural circuits will be required for new adaptive behaviors to be expressed. Yet we know little about these transitions, despite recent evidence suggesting these transitions are periods of vulnerability for initiation of pathways to pathology and developmental disorders. The purpose of this proposal is to explore developmental transitions using our model of infant rat learning. Specifically, we explore a brief 5 day period in developing rat pups when they rapidly transition between attachment learning and amygdala-dependent adult-like fear learning - both supported by odor-shock pairings - which learning system is engaged is controlled by maternal presence. In Aim 1, we test the hypothesis that prefrontal cortical (PFC) subareas' development and their control by the mother contributes to pups' ability to transition between attachment learning and amygdala-dependent fear learning. We include analysis of individual PFC-amygdala brain areas but also use a novel analytical tool to assess functional connectivity - a technique similar to fMRI analysis to facilitte translational research. Aim 2 extends these networks by testing causal roles of specific network nodes. Finally, Aim 3 examines the role of dopamine, an important modulator in PFC-amygdala function in these age- and context-dependent changes in behavioral flexibility over early development. This research has health relevance in at least two areas. First, this developmental approach assesses PFC and amygdala as individual brain areas, but also with functional connectivity analysis to go beyond defining the role of a brain area to expand our understanding of its role in a larger circuit to evoke adaptive behaviors. Indeed, both dysfunction of individual brain areas and disrupted functional connectivity have been implicated in myriad developmental disorders, including depression and ADHD. Second, this ecologically relevant approach highlights mother-infant interactions to better explain how maternal presence alters the child's behavior by expanding our understanding of how the caregiver alters brain function and neurobehavioral transitions.

描述（应用程序提供）：发展是神经行为变化的时期，需要未成熟的生物可以暴露行为灵活性以适应世界。传统开发的视图使现有的大脑电路变得越来越复杂，以适应行为改变。尽管有时确实是正确的，但其他研究表明，开发生物有时必须改变特定事件以表达更成熟行为的特定事件引起的神经回路。例如，随着婴儿从对母亲依赖到独立性的过渡，至少要表达新的自适应行为需要一些新的神经回路。然而，我们对这些过渡知之甚少，使命的最新证据表明，这些过渡是脆弱的时期，即导致病理和发育障碍的途径。该建议的目的是使用我们的婴儿大鼠学习模型探索发展过渡。具体而言，我们探索了鼠尾草在依恋学习和杏仁核依赖性的成人恐惧学习之间迅速过渡时，探索了短暂的5天，这两种学习都受到气味震颤配对的支持 - 这些学习系统均受母亲的影响控制。在AIM 1中，我们检验了以下假设：前额叶皮质（PFC）Subareas的发展及其对母亲的控制有助于PUPS在依恋学习和杏仁核依赖性恐惧学习之间过渡的能力。我们包括对单个PFC -Amygdala脑区域的分析，但还使用一种新型的分析工具来评估功能连接性 - 一种类似于fMRI分析的技术，以促进转化研究。 AIM 2通过测试特定网络节点的因果关系来扩展这些网络。最后，AIM 3研究了多巴胺的作用，多巴胺是PFC-Amygdala功能中重要的调节剂在这些年龄和上下文依赖性变化中行为灵活性在早期发展中的作用。这项研究至少在两个领域具有健康相关性。首先，这种发展方法评估PFC和Amygdala的确是单个大脑区域的两个功能障碍，但还通过功能连接性分析，无法定义大脑区域的作用，无法扩展我们对其在更大电路中的作用以唤起自适应行为的理解。大脑区域和功能连通性中断已在包括抑郁症和多动症在内的无数发育障碍中实施。其次，这种与生态相关的方法突出了母亲的相互作用，以更好地解释产妇的存在如何通过扩展我们对护理人员如何改变脑功能和神经行为转变来改变孩子的行为。