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

基本信息

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
项目类别：
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

项目摘要

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生活中的大脑可塑性产生了深远的影响。可以说有母亲护理对这一过程的影响最大，忽视导致青少年的一系列心理健康问题和成人。据估计，儿童逆境（身体虐待，忽视，粮食不安全，暴力）估计要考虑多达45％的儿童发作和32％的成人心理健康障碍。忽视是最普遍的形式美国的儿童虐待。早期生命的神经活动形状的发展，可以对大脑功能产生终生后果。前额叶皮层（PFC）正在迟到，使其更加容易受到早期逆境的影响。我们先前的研究表明，巢中的母体存在/不存在通过血清素能系统调节大鼠幼崽在产后第11天的PFC活性。在这项研究中，我们建议在成年期间测试PFC活性与行为表达之间的关系。目标 1，使用单核RNA测序，我们将测试早期逆境如何影响不同的细胞群体。此外，使用电压染料成像，我们将测试早期逆境如何影响PFC 直接和长期的活动。在AIM 2中，我们将测试PFC早期的激活或抑制PFC 生命是与母体分离相关的长期行为缺陷的因果关系。在AIM 3中，我们将测试早期生活中血清素能活性的降低是否足以产生行为缺陷在产妇分离之后观察到，最终在PFC中的5-羟色胺水平是否正常化。产妇分离可以防止行为缺陷的发展。