Sensitive Period for Neurobehavioral Development of Social Behavior

社会行为神经行为发展敏感期

基本信息

批准号：
8107557
负责人：
REGINA Marie SULLIVAN
金额：
$ 39.42万
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：
2010
资助国家：
美国
起止时间：
2010-07-10 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8107557
关键词：
Adult Adverse event Age Amygdaloid structure Anhedonia Animal Model Animals Area Autoradiography Behavior Behavioral Brain Brain region Caregivers Cell Nucleus Child Abuse Child Abuse and Neglect Childhood Collection Corticosterone Cues Data Development Early-life trauma Elderly Event Experimental Models Functional Magnetic Resonance Imaging Functional disorder Glucose Growth Human Incidence Infant Infant Behavior Lead Learning Lesion Life Limbic System Medial Mental Depression Mental Health Modeling Mothers Muscimol Prefrontal Cortex Process Publishing Rattus Shock Site Social Behavior Social Interaction Structure Swimming Symptoms Techniques Testing Time Translations Trauma Weaning Work analytical tool behavior test depressive symptoms early childhood experience infancy innovation juvenile animal maltreatment neural circuit neurobehavioral neurobehavioral test neuromechanism normal aging novel pediatric trauma postnatal public health relevance pup relating to nervous system response social tool

项目摘要

DESCRIPTION (provided by applicant): Abuse in early childhood often leads to depression, although typically not expressed until later in life. How child abuse alters the trajectory of brain development to produce a vulnerability to depression is incompletely understood. We propose to study an experimental model of parental abuse in rats where abuse during a sensitive period in infancy produces disrupted social behavior, increased immobility in a Forced Swim Test (FST) animal model of depression, and amygdala dysfunction. In this proposal we focus on the effects of abuse during infancy and early life on both behavior and brain (amygdala, prefrontal cortex). In Aim 1 we questions if there is a sensitive period of vulnerability to abuse to cause depressive-like behaviors? Aim 2 we ask if the ontogeny of the amygdala or neural circuits activated during social behavior or FST in developing rats is altered by early life abuse. In Aim 3 we question if the amygdala or prefrontal cortex or its connectivity to the PFC, which are brain areas strongly impacted by early life trauma, contribute to the behavioral dysfunction following early life abuse. The innovation and significance of our proposed work is that we use a Sensitive Period model that incorporates how the timing of perturbation (abuse) and context of perturbation (presence or absence of mother) interacts with maturational processes to enhance vulnerability to later life depressive-like symptoms. We will question how the infant brain's response to perturbation can differ depending on the time and context of perturbation and question how these experiences alter infant behaviors. This approach will enable us to not only identify infant events that contribute to later life dysfunction but also explore unique behavior and neural changes in the infant to predict later life dysfunction. We will use infants' well-defined sensitive periods for caregiver-attachment learning and infants' unique neurobehavioral response to trauma (maltreatment from mother or more controlled shock) during each period. Furthermore, this work also highlights the strong influence of social interactions and social cues (reared by abusive mother or shock with/without mother) during clearly defined sensitive periods. Indeed, our published data has begun to suggest that the infants' immediate neural response to trauma is dramatically different from the adults' but importantly, that it further differs depending on whether the mother is present. PUBLIC HEALTH RELEVANCE: Adverse experiences during childhood, such as abuse/trauma, increases the incidence of depression in later life. To better understand how this experience alters later life mental health, we use a Sensitive Period model that incorporates how the timing of perturbation (abuse) and context of perturbation (presence or absence of mother) interacts with maturational processes to enhance vulnerability to later life depressive-like symptoms.

描述（由申请人提供）：幼儿时期的虐待通常会导致抑郁，尽管通常要到晚年才会表现出来。虐待儿童如何改变大脑发育轨迹从而产生抑郁症的脆弱性尚不完全清楚。我们建议研究一种父母虐待大鼠的实验模型，其中婴儿期敏感期的虐待会导致社交行为紊乱、强迫游泳测试（FST）动物模型中抑郁症和杏仁核功能障碍的不动性增加。在本提案中，我们重点关注婴儿期和早期生活中的虐待对行为和大脑（杏仁核、前额皮质）的影响。在目标 1 中，我们质疑是否存在一个容易受到虐待而导致抑郁样行为的敏感期？目标 2 我们询问发育中的大鼠在社会行为或 FST 期间激活的杏仁核或神经回路的个体发育是否因早期生活虐待而改变。在目标 3 中，我们质疑杏仁核或前额叶皮层或其与前额皮层的连接（这些大脑区域受到早期生活创伤的强烈影响）是否会导致早期生活虐待后的行为功能障碍。我们提出的工作的创新和意义在于，我们使用敏感期模型，该模型结合了扰动（虐待）的时间和扰动的背景（母亲在场或缺席）如何与成熟过程相互作用，以增强晚年抑郁症的脆弱性症状。我们将质疑婴儿大脑对扰动的反应如何根据扰动的时间和背景而有所不同，并质疑这些经历如何改变婴儿的行为。这种方法不仅使我们能够识别导致以后生活功能障碍的婴儿事件，而且还能够探索婴儿独特的行为和神经变化，以预测以后的生活功能障碍。我们将利用婴儿明确的敏感期进行照顾者依恋学习，并利用婴儿在每个时期对创伤（母亲的虐待或更受控制的休克）的独特神经行为反应。此外，这项工作还强调了在明确定义的敏感时期，社会互动和社会线索（由虐待母亲或有/没有母亲的震惊造成的）的强烈影响。事实上，我们发表的数据已经开始表明，婴儿对创伤的直接神经反应与成人显着不同，但重要的是，它进一步取决于母亲是否在场。公共卫生相关性：童年时期的不良经历，例如虐待/创伤，会增加以后生活中抑郁症的发病率。为了更好地理解这种经历如何改变晚年的心理健康，我们使用敏感期模型，该模型结合了扰动（虐待）的时间和扰动的背景（母亲在场或缺席）如何与成熟过程相互作用，以增强晚年抑郁的脆弱性类似症状。