NEURODEVELOPMENT /NEURODISORDER

这个小组的长期目标是建立一个多人调查人员， 跨学科研究计划，重点是儿童精神障碍 发育中的神经系统。这类障碍将包括智力低下。 儿童期和成年期的症状、学习和行为障碍 发作性精神障碍，其发展基础很强 根据当前研究文献提出的建议。 目前的建议是基于先前对小鼠的初步研究。 活动负责人和合作者表现出的行为和 小鼠的结构性二型性并提示其易感性 传入大脑皮层发育变化的这种二形性 调制系统。本提案的重点是研究 神经调节性神经递质与发育的关系 乙酰胆碱、去甲肾上腺素、多巴胺和5-羟色胺 在这个小鼠模型中，性激素和皮质形态发生。这个 我们要检验的假设是小鼠的结构性性别差异 大脑皮层和伴随的行为差异导致 皮质个体发育的神经调节调节改变。为了测试这一点 假设我们将1)评估大脑皮质细胞结构的变化 选择性阻断特异性受体引起的雄性和雌性小鼠 神经调节系统正在开发中；这将需要开发 选择性抑制剂，Hajjii博士，Dep.化学；2)测定 神经调节剂水平或纤维时间是否存在性别差异 大脑皮层个体发育过程中的内向生长；(3)实验测试 发育过程中荷尔蒙水平的改变会影响个体发育 雄性和雌性小鼠的神经调节系统；4)开始研究 性激素和神经调节剂影响的分子机制 形态发生和随后的行为；5)开始一项先导研究，以评估 不良应激和环境毒素是否影响相互作用 性激素和神经调节化学之间的关系，导致改变 行为功能。 由于许多发育性中枢神经系统疾病影响男性和女性 脑内性二型性个体发育的辨证 皮质将帮助我们更好地了解此类疾病的病因。 此外，拟议的研究旨在使 神经障碍/神经发育小组加大研究力度 现有教员的能力、基础设施和支持 通过增加更多的教员专业知识和通过 与其他领域的研究人员共同开发跨学科项目 纪律和制度。

The long-term goal of this group is to establish a multi-investigator, interdisciplinary research program with focus on disorders of the developing nervous system. Such disorders will include mental retardation syndromes, learning and behavioral disorders of childhood onset and adult onset psychiatric disorders for which a developmental basis is strongly suggested by current research literature. The current proposal is based on previous and preliminary studies in mouse by the activity leader and collaborators that have shown behavioral and structural sexual dimorphism in mice and suggested the susceptibility of this dimorphism to developmental alterations in afferent cortical modulatory systems. The focus of the present proposal is to study the developmental relationships between the neuromodulatory neurotransmitters acetylcholine [ACh], norepinephrine [NE], dopamine [DA], and serotonin [5- HT], sex hormones and cortical morphogenesis in this mouse model. The hypothesis we aim to test is that structural sex differences in mouse cerebral cortex and accompanying differences in behavior result from altered neuromodulatory regulation of cortical ontogeny. To test this hypothesis we will 1) assess alterations in cortical cytoarchitecture of male and female mice resulting from selective block of specific neuromodulator systems in development; this will entail the development of selective inhibitors by Dr. Hajjii, Dept. of chemistry; 2) determine whether there are sex differences in neuromodulator level or time of fiber ingrowth during ontogeny of cerebral cortex; (3) test how experimentally altered hormonal levels in development affect the ontogeny of the neuromodulator systems in male versus female mice; 4) begin to study molecular mechanisms through which sex hormones and neuromodulators impact morphogenesis and subsequent behavior; 5) begin a pilot study to assess whether adversive stress and environmental toxins affect the interactions between sex hormones and neuromodulatory chemistry, resulting in altered behavioral function. Since many CNS disorders with developmental onset affect male and females differentially, elucidating the ontogeny of sexual dimorphism in cerebral cortex will help us to better understand the etiology of such disorders. Furthermore, the proposed studies are designed to enable the Neurodisorder/Neurodevelopment group to increase the research capabilities, infrastructure and support for existing faculty as well as expand the research scope by adding additional faculty expertise and by developing interdisciplinary projects with investigators in other disciplines and institutions.