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？

• 批准号: 9197675
• 负责人: LEAH ANN KRUBITZER
• 金额: $ 39.09万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 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/9197675
• 关键词: Adolescence; Adolescent; Adopted; Adult; Adult Children; Affect; Anatomy; 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; Human; ID2 gene; Impairment; Individual Differences; Infant; Inherited; Investigation; Laboratories; Life; Life Experience; Link; Mammals; Measures; Mediating; Mental Health; Microtus; Modification; Mothers; Motivation; Neocortex; Nurses; 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; public health relevance; social; somatosensory

 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（由申请人提供）：为什么我们早期的互动，尤其是与父母的互动，会对后来的社会行为以及我们如何抚养自己的孩子产生如此巨大的影响？有压倒性且明确的证据表明，生命早期异常的亲子互动，包括虐待和虐待，会对青少年的行为结果产生负面影响，并使虐待或虐待的持续循环永久化。然而，很少有研究将这些早期经历与大脑组织和连接的变化直接联系起来。此外，人们对发育过程中产生这些大脑解剖学变化的潜在遗传和表观遗传机制知之甚少。该提案的总体目标是确定由体感和嗅觉系统介导的早期社会互动如何影响特定连接模式的发展，从而在人群中产生个体差异。我们使用一种独特的动物模型，即草原田鼠，它是少数一夫一妻制、配对并双亲抚养幼崽的哺乳动物之一。配对父母在教养方式上表现出显着的差异，特别是在需要密切身体接触的行为方面，例如护理、挤在一起和非挤在一起接触，所有这些都深刻地塑造了触觉和嗅觉体验。我们量化了这些抚养方式的差异，并证明了后代的皮质连接和社会行为的显着差异 高接触（HC）和低接触（LC）父母。此外，LC 和 HC 后代采用与其父母相似的抚养方式，从而延续了这两种不同的表型。后代的交叉抚养表明，这些行为变化是“文化上”遗传的，而不是遗传的。这开启了一个有趣的可能性，即在很大程度上，经验产生了与不同行为相关的皮质连接的差异。换句话说，大脑组织的某些方面可能是通过文化传播的。然而，差异性感官体验、父母教养方式和大脑皮层连接之间的直接关系尚未建立。在人类、啮齿动物和许多其他哺乳动物中，早期的触觉和嗅觉体验对于在母亲和后代之间形成孝顺关系以及在以后的生活中建立正常的社会行为至关重要。因此，我们对田鼠的研究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，我们将交叉培养 HC 和 LC 后代；在其中一些窝中，我们会诱发嗅觉丧失症。在所有组中，我们将比较交叉寄养的后代与其寄养兄弟姐妹和亲生兄弟姐妹的几项指标，包括：嗅觉和触觉辨别、社会行为以及体感（S1）、嗅觉（眶额皮质，OFC）和前扣带回（ACC）皮质区域连接的密度和分布。最后，我们将确定连接发生改变的发育时期，并探索驱动皮质连接变化的一些遗传和表观遗传机制。通过这种设计，我们将揭示将早期感官体验转化为皮质表型的机制，从而在以后的生活中产生适应性和复杂的社会行为。