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：
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
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/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

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（由申请人提供）：为什么我们的早期互动，尤其是与父母的互动，对后来的社会行为以及我们如何养育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，早期的亲子互动存在异常。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。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。该提案的首要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。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、配对且双亲抚养幼崽的哺乳动物之一。配对父母在养育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，我们已经量化了这些养育方式的差异。后代的皮质连接和社会行为表现出显着差异此外，LC 和 HC 的后代采用与其父母相似的养育方式，使这两种不同的表型永久存在，后代的这些行为变化表明。这揭示了一种有趣的可能性，即在很大程度上，经验产生了与不同行为相关的皮层连接的差异。换句话说，大脑组织的某些方面可能是通过文化传播的。之间的直接关系在人类、啮齿动物和许多其他哺乳动物中，不同的感官体验、父母养育方式和大脑皮层连接性尚未建立，早期的触觉和嗅觉体验对于母亲和后代之间形成孝顺关系以及建立正常的社会关系至关重要。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。在所有组中，我们将比较交叉寄养的后代与他们的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）连接的密度和分布。最后，我们将确定连接发生变化的发育时期，并探索一些遗传和表观遗传。通过这种设计，我们将揭示将早期感官体验转化为皮层表型的机制，从而在以后的生活中产生适应性和复杂的社会行为。