Sensitive Period for Neurobehavioral Development of Social Behavior

社会行为神经行为发展敏感期

• 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
• 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

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症，尽管通常要等到生命后期才表达。虐待儿童如何改变大脑发育的轨迹，从而使抑郁症的脆弱性尚不完全理解。我们建议研究大鼠父母虐待的实验模型，在婴儿期间敏感时期的虐待会导致社会行为破坏，在强迫游泳测试（FST）抑郁症动物模型和杏仁核功能障碍中的固定性增加。在此提案中，我们着重于婴儿期和早期生命期间的虐待对行为和大脑的影响（杏仁核，前额叶皮层）。在AIM 1中，我们质疑是否存在敏感的虐待时期，以引起抑郁症的行为？ AIM 2我们询问我们在社会行为或FST中激活的杏仁核或神经回路的个体是否因早期生命虐待而改变。在AIM 3中，我们质疑杏仁核或前额叶皮层或与PFC的连通性是由早期生命创伤强烈影响的大脑区域，导致早期生活滥用后的行为功能障碍。我们提出的工作的创新和意义在于，我们使用一个敏感的时期模型，该模型结合了扰动时间（滥用）的时间和扰动（母亲的存在或不存在）与成熟过程相互作用，以增强对以后生活抑郁症状症状的脆弱性。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行为。这种方法将使我们不仅能够确定有助于以后生命功能障碍的婴儿事件，还可以探索婴儿的独特行为和神经变化，以预测以后的生活功能障碍。我们将在每个时期使用婴儿定义明确的敏感时期进行护理人员 - 跟踪学习和婴儿对创伤的独特神经行为反应（母亲虐待或更受控的休克）。此外，这项工作还强调了在明确定义的敏感时期，社会互动和社会暗示（由虐待母亲或没有母亲的震惊）的强烈影响。的确，我们已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年人截然不同。 公共卫生相关性：童年时期的不利经历，例如虐待/创伤，会增加后来生活中抑郁症的发病率。为了更好地了解这种经验如何改变以后的生活心理健康，我们使用敏感的时期模型，该模型结合了扰动（滥用）的时机和扰动（母亲的存在或不存在）与成熟过程相互作用，以增强对以后生活抑郁症状症状的脆弱性。