How Does Early Sensory Experience Affect Cortical Connections and Behavior?

早期感官体验如何影响皮质连接和行为？

基本信息

批准号：
9030107
负责人：
LEAH ANN KRUBITZER
金额：
$ 39.03万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-18 至 2020-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9030107
关键词：
Adolescence Adolescent Adopted Adult Adult Children Affect Animal Model Animals Anosmia Anterior Area Behavior Behavioral Biological Brain Characteristics Child Child Abuse Child Behavior Child Rearing Complex Development Discipline of Nursing Discrimination Early Intervention Environment Ephrin-A5 Epigenetic Process Exhibits Female Fostering Gene Expression Gene Expression Profile Generations Genes Genetic Genetic Transcription Goals Health Human ID2 gene Individual Differences Infant Inherited Investigation Laboratories Life Life Experience Link Mammals Measures Mediating Mental Health Microtus Modification Mothers Motivation Neocortex Olfactory Pathways Outcome Pair Bond Parent-Child Relations Parents Pattern Perception Phenotype Play Population Process Promoter Regions Risk Rodent Role Sensory Shapes Siblings Smell Perception Social Behavior Social Discrimination Social Interaction Solid Somatosensory Cortex Substance abuse problem Tactile Time Translating Violence base behavioral outcome chromatin modification chromatin remodeling cingulate cortex density design early experience experience foster parent histone modification male maltreated children maltreatment neocortical neurodevelopment offspring postnatal prairie vole protein expression social somatosensory

项目摘要

DESCRIPTION (provided by applicant): Why do our early interactions, particularly those with our parents, have such an enormous impact on subsequent social behavior and how we rear our own children? There is overwhelming and unequivocal evidence that aberrant parent-offspring interactions during early life, including maltreatment and abuse, negatively impact adolescent behavioral outcomes and perpetuate a continuing cycle of abuse or maltreatment. However, there are few, if any, studies that have directly linked these early experiences to changes in brain organization and connectivity. Further, the underlying genetic and epigenetic mechanisms present during development that generate these anatomical changes to the brain are only poorly understood. The overarching goal of this proposal is to determine how early social interactions, mediated by somatosensory and olfactory systems, impact the development of specific patterns of connectivity to produce individual differences within a population. We use a unique animal model, the prairie vole, which is one of only a small proportion of mammals that are monogamous, pair-bonded and that rear their young bi-parentally. Pair-bonded parents show remarkable variability in rearing styles, particularly in behaviors requiring close physical contact such as nursing, huddling, and non-huddling contact, all of which profoundly shape tactile and olfactory experience. We have quantified these differences in rearing style, and have demonstrated significant differences in cortical connectivity and social behaviors of the offspring of high contact (HC) and low contact (LC) parents. In addition, LC and HC offspring adopt a similar rearing style to that of their parents, perpetuating these two distinct phenotypes. Cross-fostering of offspring demonstrates that these changes in behavior are "culturally" transmitted rather than inherited. This opens up the intriguing possibility that, in large part, experience generates the differences in cortical connectivity associated with the different behaviors. In othe words, some aspects of brain organization may be culturally transmitted. However, a direct relationship between differential sensory experience, parental rearing styles, and cortical connectivity of the brain has never been established. In humans, rodents and many other mammals, early tactile and olfactory experience is critical for forming filial relationships betwee the mother and the offspring and for establishing normal social behavior later in life. Thus, results from our studies in voles have broad implications for mammals in general, including humans. In these studies we will cross-foster HC and LC offspring; in some of these litters we will induce anosmia. In all groups we will compare cross-fostered offspring with their in-fostered siblings and their biological siblings on several measures including: olfactory and tactile discrimination, social behavior, and density and distribution of connections of somatosensory (S1), olfactory (orbitofrontal cortex, OFC), and anterior cingulate (ACC) cortical areas. Finally, we will determine the period in development when alterations in connectivity occur, and explore some of the genetic and epigenetic mechanisms that drive these changes in cortical connectivity. With this design we will reveal the mechanisms that translate early sensory experiences into a cortical phenotype that generates adaptive, and complex social behavior later in life.

描述（由适用提供）：为什么我们的早期互动，尤其是与父母的互动，对随后的社会行为以及我们如何养育自己的孩子产生如此大的影响？有压倒性和明确的证据表明，早期生命中的父母相互作用异常，包括虐待和虐待，对青少年行为结果产生负面影响，并使持续的虐待或虐待循环永存。但是，很少有（如果有的话）将这些早期经验与大脑组织和连通性的变化联系起来。此外，在发育过程中存在的基本遗传和表观遗传机制对大脑产生这些解剖学变化只有很少的了解。该提案的总体目标是确定早期社会互动是如何通过体感和嗅觉系统介导的，影响了特定连通性模式的发展，以在人群中产生个体差异。我们使用独特的动物模型，大草原vole，这是一夫一妻制，成对绑定且双方幼年的哺乳动物中仅有的一小部分。成对的父母在饲养方式中表现出显着的差异，尤其是在需要紧密接触的行为中，例如护士，huddling和非烦恼的接触，所有这些都深刻地塑造了触觉和嗅觉经验。我们已经量化了饲养方式的这些差异，并在后代的皮质连通性和社会行为上表现出显着差异高接触（HC）和低接触（LC）父母此外，LC和HC后代采用与父母相似的饲养方式，使这两种不同的表型永存。后代的交叉促进表明，行为上的这些变化是“文化上”传播而不是继承的。这打开了一种有趣的可能性，即在很大程度上，经验会产生与不同行为相关的皮质连通性的差异。词，大脑组织的某些方面可能是文化传播的。但是，从未建立不同的感觉体验，父母饲养方式和大脑的皮质连通性之间的直接关系。在人类，啮齿动物和许多其他哺乳动物中，早期的触觉和嗅觉经验对于在母亲和后代建立fil骨关系以及在以后的生活中建立正常的社会行为至关重要。这是我们对VOL研究的结果对包括人类在内的一般哺乳动物具有广泛的影响。在这些研究中，我们将交叉促进HC和LC后代。在其中一些垃圾中，我们将诱发厌食症。 In all groups we will compare cross-fostered offspring with their in-fostered siblings and their biological siblings on several measures including: olfactory and tactile discrimination, social behavior, and density and distribution of connections of somatosensory (S1), olfactory (orbitofrontal cortex, OFC), and anterior cingulate (ACC) cortical areas.最后，我们将确定发生连通性改变的开发期，并探索一些驱动皮质连通性变化的遗传和表观遗传机制。通过这种设计，我们将揭示将早期感觉体验转化为一种皮质表型的机制，该表型会在以后的生活中产生适应性和复杂的社会行为。