How Does Early Sensory Experience Affect Cortical Connections and Behavior?

 描述(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养育自己的孩子有如此巨大的影响？有确凿的证据表明，早期生活中异常的亲子互动，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，在发育过程中产生这些大脑解剖变化的潜在遗传和表观遗传机制还知之甚少。这项建议的首要目标是确定早期的社会互动是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的，这些互动由体感和嗅觉系统调节。我们使用了一种独特的动物模型--草原田鼠，它是为数不多的一夫一妻、成对结合、双亲抚养幼崽的哺乳动物之一。结对父母在养育方式上表现出显著的差异，特别是在需要密切身体接触的行为上，如哺乳、抱抱和非抱抱接触，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，并显示出后代在大脑皮层连接和社会行为方面的显著差异 高接触(HC)和低接触(LC)双亲。此外，LC和HC后代采用与双亲相似的饲养方式，使这两种不同的表型永久化。对后代的交叉养育表明，这些行为变化是“文化”传递的，而不是遗传的。这开启了一种有趣的可能性，即在很大程度上，经验导致了与不同行为相关的大脑皮层连接性的差异。换句话说，大脑组织的某些方面可能是文化传递的。然而，不同的感觉体验、父母的教养方式和大脑的皮质连接之间的直接关系从未得到证实。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子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都有广泛的影响。在这些研究中，我们将交叉寄养HC和LC后代；在其中一些后代中，我们将导致嗅觉丧失。在所有组中，我们将比较交叉寄养的后代和他们的寄养兄弟姐妹及其亲生兄弟姐妹的几个指标，包括：嗅觉和触觉辨别、社会行为以及躯体感觉(S1)、嗅觉(OFC)和前扣带(ACC)皮质区的连接密度和分布。最后，我们将确定发生连接性变化的发育阶段，并探索驱动这些皮质连接性变化的一些遗传和表观遗传机制。通过这个设计，我们将揭示将早期感觉经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的和复杂的社会行为。

 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.