Hormones, Experience and Hippocampal Neurogenesis

描述(由申请人提供)：这项建议的广泛的、长期的目标是更好地了解成年海马区神经发生的功能。为了实现这一总体目标，将使用以下方法：1)研究社会和空间复杂经历对新神经元、激素水平和学习的影响；2)探索睡眠、新神经元和学习之间的相互作用；3)确定新神经元枯竭对海马体功能的影响；以及4)表征成熟和未成熟神经元之间的差异。生活在标准的实验室条件下对海马区新神经元的存活有深远的负面影响。因此，提出的实验的一个主要目标是确定一个自然的、相对复杂的环境中对海马神经发生重要的元素。将用溴脱氧尿嘧啶核苷(BrdU)标记结合免疫细胞化学来评估海马区新细胞的产生、存活和表型，通过放射免疫法评估激素水平，并通过各种联想学习任务来评估海马区的功能，包括痕迹眨眼条件作用、痕迹恐惧条件作用、情景恐惧条件作用和在Morris水迷宫中的空间学习。这些技术将应用于那些经历过不同社会经历、被剥夺了不同阶段睡眠或药物导致新神经元枯竭的动物。最后一系列研究将检验成年期产生的神经元与发育期间产生的神经元的结构和生化特征。这些实验将使用神经解剖学示踪结合BrdU标记，电子显微镜结合~3H-胸腺嘧啶核苷标记和共聚焦显微镜。由于压力、睡眠和海马体与几种精神疾病有关，其中许多都有认知成分，这些结果可能会阐明精神病理学发展背后的大脑机制。

DESCRIPTION (provided by applicant): The broad, long-term objective of this proposal is to gain a better understanding of the function of adult neurogenesis in the hippocampus. The following approaches will be used to achieve this general goal: 1) examination of the impact of socially and spatially complex experiences on new neurons, hormones levels and learning; 2) Exploration of the interaction between sleep, new neurons and learning; 3) determination of the impact of new neuron depletion on hippocampal function; and 4) characterization of differences between mature and immature neurons. Living under standard laboratory conditions has a profound negative impact on the survival of new neurons in the hippocampus. Therefore, a major goal of the experiments proposed is to identify the elements of a naturalistic, relatively complex environment that are important for hippocampal neurogenesis. The production, survival and phenotype of new cells in the hippocampus will be assessed with bromodeoxyuridine (BrdU) labeling combined with immunocytochemistry for cell-type specific markers, hormone levels will be assessed via radioimmunoassay and hippocampal function will be assessed by a variety of associative learning tasks, including trace eyeblink conditioning, trace fear conditioning, context fear conditioning and spatial learning in a Morris water maze. These techniques will be applied to animals that have been exposed to different social experiences, deprived of different stages of sleep or pharmacologically depleted of new neurons. A final series of studies will examine the structural and biochemical characteristics of neurons generated in adulthood compared to those generated during development. These experiments will use neuroanatomical tract tracing combined with BrdU labeling, electron microscopy combined with 3H-thymidine labeling and confocal microscopy. Because stress, sleep and the hippocampus have been linked to several psychiatric conditions, many of which have a cognitive component, these results may elucidate the brain mechanisms that underlie the development of psychopathology.