Embedding of Parental Experience within the Offspring Telencephalon

生命早期的不良经历可以极大地改变一个人在以后的生活中出现健康问题的风险;然而，我们对这种关系如何形成的理解仍然很差。因此，拟议的研究计划旨在探索父母所经历的压力如何影响大脑中已知对创造新记忆至关重要的区域的发展。 我们已经证明，出生前（以母亲肥胖的形式）和儿童时期（以社会孤立的形式）的逆境都可以“深入皮肤”，影响大脑发育，特别是海马体（对记忆形成很重要的区域）。例如，我们发现肥胖母亲的后代在空间学习的某些行为测量中表现出显着的年龄和性别相关障碍，并且早期社会隔离影响某些可塑性相关蛋白质的表达，而不会改变空间记忆。 这项工作的长期目标将是继续建立一个研究计划，使用“细胞到行为”的角度来研究各种形式的早期生活经验如何影响大脑发育。 指导当前提案的短期目标是：1）研究在生命周期的不同阶段，心理社会压力如何影响与记忆形成相关的蛋白质、细胞过程和行为。 2)扩大我们的视野，考虑父亲的逆境可能对大脑发育的作用。 3)研究父母的逆境如何影响海马体和前额叶皮层（另一个重要的学习和记忆区域）。 根据所述目标，该建议将：1）描述继发性创伤应激模型对成人大脑的影响。我们将研究可塑性相关蛋白的变化，可塑性的电生理措施，以及雄性和雌性大鼠的行为表型。 2)检查父母暴露于继发性创伤应激可能对后代大脑的影响。雄性大鼠（怀孕前）和雌性大鼠（在怀孕的不同阶段）将经历压力，并在不同年龄对后代进行检查。 3)探索早期生活中的逆境是否会增强面对成年压力源的弹性。在怀孕期间，雌性大鼠将经历标准的住房条件，或暴露于二次创伤应激，它们的后代将继续经历类似的成年环境，或不匹配的环境。 预期意义这项工作将扩大我们对早期生活逆境如何改变与记忆形成相关的大脑区域发育的理解。此外，有机会解决复杂的翻译问题，以及我们采用的“细胞到行为”的方法，应该提供一个独特的和引人入胜的学生培训环境。

GENERAL SUMMARY Adverse experiences early in life can greatly alter a person's risk for health problems later in life; however, our understanding of exactly how this relationship takes shape remains poor. As a result, the proposed research programme aims to explore the way that stressors experienced by parents can affect the development of those areas of the brain known to be important for creating new memories. RECENT PROGRESS We have shown that adversity both before birth (in the form of maternal obesity) and during childhood (in the form of social isolation) can "get under the skin" to affect brain development, particularly within the hippocampus (a region important to memory formation). For example, we discovered offspring of obese mothers show significant age and sex-related impairments in certain behavioural measures of spatial learning, and that early--life social isolation affects the expression of certain plasticity--related proteins without altering spatial memory. RESEARCH OBJECTIVES The long-term objective of this work will be to continue building a research programme that uses a "cell to behaviour" perspective to examine how various forms of early-life experience affect brain development. The short term objectives guiding the current proposal are to: 1)examine how psychosocial stress at different points in the lifespan affects proteins, cellular processes, and behaviours related to memory formation. 2)expand our view to consider the role that paternal adversity may have upon brain development. 3)investigate the way in which parental adversity affects both the hippocampus and the pre-frontal cortex (another area important for mediating learning and memory). SUMMARY OF PLANNED EXPERIMENTS Following from the stated objectives, the proposal will: 1)Characterise the effect that a model of secondary traumatic stress can have upon the adult brain. We will examine changes in plasticity-related proteins, electrophysiological measures of plasticity, and the behavioural phenotype of male and female rats. 2)Examine the influence that parental exposure to secondary traumatic stress may have upon the offspring brain. Male rats (before conception) and female rats (at different stages of pregnancy) will experience stress, and offspring will be examined at different ages. 3)Explore whether early-life adversity enhances resiliency in the face of an adult stressor. During gestation, female rats will experience either standard housing conditions, or exposure to secondary traumatic stress and their offspring will go on to experience either a similar adult environment, or a mismatched one. EXPECTED SIGNIFICANCE The proposed work will expand our understanding of how early-life adversity alters the development of brain regions related to memory formation. In addition, the opportunity to tackle complex, translational questions, and our adoption of a "cell to behaviour" approach, should provide a unique and engaging student training environment.