How Does Early Sensory Experience Affect Cortical Connections and Behavior?

 描述（由申请人提供）：为什么我们早期的互动，特别是与父母的互动，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？有压倒性和明确的证据表明，在生命早期父母与子女的异常互动，包括虐待和虐待，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，在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。这项建议的总体目标是确定早期的社会互动，介导的躯体感觉和嗅觉系统，影响特定模式的连接的发展，以产生人口中的个体差异。我们使用一种独特的动物模型，草原田鼠，这是一个只有一小部分的哺乳动物，是一夫一妻制，对债券和抚养他们的年轻双亲。成对结合的父母在养育方式上表现出显着的变化，特别是在需要密切身体接触的行为上，如护理，蜷缩和非蜷缩接触，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，并证明了后代在皮层连接和社会行为方面的显着差异 高接触（HC）和低接触（LC）的父母。此外，LC和HC的后代采用类似的饲养方式，他们的父母，延续这两个不同的表型。后代的交叉培养表明，这些行为变化是“文化”传播的，而不是遗传的。这开启了一个有趣的可能性，在很大程度上，经验产生了与不同行为相关的皮层连接差异。换句话说，大脑组织的某些方面可能是文化传播的。然而，差异的感觉经验，父母养育方式和大脑皮层连接之间的直接关系从未建立。在人类、啮齿动物和许多其他哺乳动物中，早期的触觉和嗅觉经验对于母亲和后代之间形成亲子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，我们在田鼠中的研究结果对包括人类在内的哺乳动物具有广泛的意义。在这些研究中，我们将交叉培养HC和LC后代;在其中一些窝仔中，我们将诱导嗅觉丧失。在所有组中，我们将比较交叉寄养的后代与他们的寄养兄弟姐妹和他们的生物学兄弟姐妹在几个措施，包括：嗅觉和触觉的歧视，社会行为，和密度和分布的体感（S1），嗅觉（眶额皮质，OFC），和前扣带（ACC）皮质区的连接。最后，我们将确定发育过程中连接性发生变化的时期，并探索推动皮质连接性这些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觉经验转化为皮质表型的机制，该表型在以后的生活中产生适应性和复杂的社会行为。

 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.