Hippocampal neurogenesis and remodeling

早期生活中的压力经历与下丘脑-垂体-肾上腺（HPA）轴异常、行为改变和精神病理的发展有关。研究大脑中发生的细胞变化对发育压力的反应可能会使我们更接近于理解这些功能后果背后的机制。本中心拨款提案中的其他项目旨在从分子到行为的各个分析层面探索压力引起的大脑变化。这个项目将研究早期生活中令人厌恶的经历对大脑结构的影响。这里提出的研究集中在海马体区域，这是一个对压力敏感的区域，与精神病理有关，包括抑郁症和创伤后应激障碍。海马体区域在出生后经历了广泛的发育，这可能使该结构对环境扰动具有潜在的脆弱性。特别是，齿状体的颗粒神经元群主要在出生后形成。事实上，从啮齿类动物到灵长类动物，大多数哺乳动物在成年后都会产生这些细胞。先前的研究表明，这些海马神经元的产生在成年期受到压力的抑制。本研究的目的是利用研究中心提供的啮齿类动物和灵长类动物模型（PI, Plotsky）， （PI, Insel），探讨延长早期生活应激对颗粒神经元群体、CA3锥体神经元群体以及这两种细胞群之间苔藓纤维连接的发育的影响。通过BrdU标记、3h -胸腺嘧啶放射自显影、免疫细胞化学、高尔基浸渍和神经解剖道示踪等多种组织学方法，探讨早期生活应激对海马神经元形成和维持的影响。这些研究将有助于中心的总体目标，即更好地了解早期生活压力对大脑结构和功能的影响，并最终促进精神病理学的发展。

Stressful experiences during early life have been associated with abnormalities in the hypothalamicpituitary-adrenal (HPA) axis, changes in behavior and the development of psychopathology. Studying the cellular changes that occur in the brain in response to developmental stressors may bring us closer to understanding the mechanisms that underlie these functional consequences. Other projects in this Center grant proposal are designed to explore stress-induced changes in the brain at various levels of analysis, from molecular to behavioral. This project will examine the impact of aversive experience during early life on the structure of the brain. The studies proposed here focus on the hippocampal region, an area that is sensitive to stress and has been implicated in psychopathologies, including depression and posttraumatic stress disorder. The hippocampal region undergoes extensive development during the postnatal period that may render this structure potentially vulnerable to environmental perturbations. In particular, the granule neuron population of the dentate gyms is formed predominantly during the postnatal period. In fact, the production of these cells extends well into adulthood in most mammals, from rodents to primates. Previous studies have shown that the production of these hippocampal neurons is suppressed by stress in adulthood. This proposal is designed to explore the consequences of prolonged early life stress on the development of the granule neuron population, the CA3 pyramidal neuron population and the mossy fiber connections between these two cell groups using the rodent and primate models provided by the cores (PI, Plotsky), (PI, Insel). Using a variety of histological methods, including BrdU labeling, 3H-thymidine autoradiography, immunocytochemistry, Golgi impregnation and neuroanatomical tract tracing, the impact of early life stress on the formation and maintenance of hippocampal neurons will be explored. These studies will contribute to the Center's overall purpose to gain a better understanding of the effects of early life stress on brain structure and function and, ultimately, to the development psychopathology.