Role of PFC Activity in the Behavioral Deficits Induced by Maternal Separation

PFC 活性在母亲分离引起的行为缺陷中的作用

• 批准号: 10567520
• 负责人: Catia Teixeira
• 金额: $ 48.58万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-11 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10567520
• 关键词: Adaptive Behaviors; Adolescent; Adult; Affect; Anterior; Attention; Attentional deficit; Behavior; Behavioral; Bipolar Disorder; Brain; Caring; Cells; Child; Child Abuse and Neglect; Childhood; Data; Development; Dyes; Enterobacteria phage P1 Cre recombinase; Environment; Environmental Risk Factor; Exposure to; Fluoxetine; Frequencies; Functional disorder; Gene Expression; Image; Impaired cognition; Impulsivity; Ketanserin; Knowledge; Life; Link; Location; Major Depressive Disorder; Maternal Behavior; Memory; Mental Health; Mental disorders; Mothers; Mus; Neurons; Newborn Infant; Pathway interactions; Population; Post-Traumatic Stress Disorders; Predisposition; Prefrontal Cortex; Process; Rattus; Reaction Time; Regulation; Risk; Rodent; Role; Schizophrenia; Selective Serotonin Reuptake Inhibitor; Serotonergic System; Serotonin; Shapes; Signal Transduction; Syndrome; Testing; Transgenic Mice; United States; Violence; Viral Vector; behavior test; behavioral outcome; caregiving; cell cortex; child neglect; childhood adversity; cingulate cortex; constriction; designer receptors exclusively activated by designer drugs; early life adversity; early life stress; executive function; food insecurity; inhibitor; maladaptive behavior; maternal separation; neglect; nerve supply; neural; novel; object recognition; optogenetics; pediatric trauma; physical abuse; postnatal; postnatal period; prepulse inhibition; prevent; pup; receptor; response; single nucleus RNA-sequencing; stressor; transcriptome; voltage; voltage sensitive dye

Project Summary Environmental factors have profound influence on brain plasticity during early-life. Maternal care arguably has the greatest influence on this process, with neglect resulting in an array of mental health issues in adolescents and adults. Childhood adversity (physical abuse, neglect, food insecurity, violence) is estimated to account for up to 45% of child-onset and 32% of adult-onset mental health disorders. Neglect is the most prevalent form of childhood maltreatment in the United States. Neural activity in early life shapes circuit development and can have lifelong consequences on brain function. The prefrontal cortex (PFC) is late-developing, making it more susceptible to early-life adversity. Our previous study revealed that maternal presence/absence from the nest regulates the activity of the PFC of rat pups at postnatal day 11 via the serotonergic system. In this study, we propose to test the relation between PFC activity during early-life and behavioral expression in adulthood. In Aim 1, using single nucleus RNA sequencing, we will test how early-life adversity affects the expression profile of distinct cell populations. Furthermore, using voltage dye imaging, we will test how early-life adversity affects PFC activity in the immediate and long-term. In Aim 2, we will test whether activation or inhibition of the PFC in early- life is causal or protective of long-term behavioral deficits associated with maternal separation. In Aim 3, we will test whether a decrease in serotonergic activity during early-life is sufficient to produce the behavioral deficits observed after maternal separation and, ultimately, whether normalizing serotonin levels in the PFC during maternal separation can prevent the development of behavioral deficits.

项目摘要 环境因素对早期大脑的可塑性有深远的影响。产妇保健可以说是有 对这一过程影响最大的是忽视，导致青少年出现一系列心理健康问题 和成年人。据估计，童年时期的逆境(身体虐待、忽视、食物不安全、暴力)是 高达45%的儿童发病精神健康障碍和32%的成人发病精神健康障碍。忽视是最普遍的形式 美国的儿童期虐待。早期生命中的神经活动塑造了电路发育，并可以 会对大脑功能产生终生影响。前额叶皮质(PFC)发育较晚，使其 易受早年逆境影响的。我们之前的研究表明，母体的存在/离开巢 通过5-羟色胺能系统调节出生后11天仔鼠PFC的活性。在这项研究中，我们 建议测试早期PFC活动与成年后行为表达之间的关系。在AIM 1、利用单核RNA测序，我们将测试早期生活逆境如何影响 不同的细胞群。此外，使用电压染料成像，我们将测试早期生活中的逆境如何影响PFC 当前和长期的活动。在目标2中，我们将测试早期PFC的激活或抑制。 生活是与母亲分离相关的长期行为缺陷的原因或保护。在《目标3》中，我们将 测试早期5-羟色胺能活动减少是否足以产生行为缺陷 在母体分离后观察，最终在PFC中是否使5-羟色胺水平正常化 母体分离可以防止行为缺陷的发展。