ABNORMAL ONTOGENY AND CORTICAL FUNCTION IN A MOUSE MODEL

小鼠模型中异常的个体发育和皮质功能

• 批准号: 6107932
• 负责人: CHRISTINE F HOHMANN
• 金额: $ 15.57万
• 依托单位: MORGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107932
• 关键词: antisense nucleic acid; behavior disorders; behavior test; behavioral /social science research tag; brain injury; cell death; cell differentiation; cerebral cortex; cholinergic receptors; cognition disorders; densitometry; developmental neurobiology; experimental brain lesion; high performance liquid chromatography; histogenesis; image processing; immunocytochemistry; immunotoxicity; injection /infusion; laboratory mouse; neural transmission; neuroanatomy; neurochemistry; neurons

Early insult or injury to the brain is involved in many debilitating developmental disorders including severe learning disabilities and mental retardation. A common feature of many of these disorders is abnormal morphogenesis of the cerebral cortex. Clinical observers have long presumed that abnormal cortical cytomorphology is responsible for the behavioral changes and cognitive deficits in developmental brain disorders. However, few attempts have been made to experimentally test this hypothesis. Here we utilizes a mouse model to address the hypothesis that abnormal cortical cytomorphology can be correlated with impaired cognitive behavior. In mice, cholinergic projections from the nucleus basalis area [nBM] invade neocortex at birth and are temporally and spatially well suited to play a modulatory role in morphogenesis. When lesions are performed in the nBM area at birth, a transient depletion of cortical cholinergic markers ensues which is accompanied by retarded neuronal maturation. Cortical cytoarchitecture and connectivity remain permanently altered into adulthood despite cholinergic re-innervation of neocortex. Recent behavioral experiments with mice that received bilateral nBM lesions at birth show deficits in memory and learning in these animals by adulthood. Preliminary results suggest that these behavioral deficits are correlated with specific morphological and neurochemical features in cerebral cortex. This project is designed to l) examine and quantify the key morphological and neurochemical features in the cortex of neonatally nBM lesioned mice after they have concluded behavioral testing in early adulthood; these data will than be examined for correlations with behavioral testing scores; 2) to investigate whether abnormal cortical morphogenesis following neonatal lesions to the nBM area in mouse is the result of selective depletion of cholinergic afferent fibers and/or neurotransmission and 3) to train minority students in basic laboratory and research skills through their participation in a biomedically relevant research project

大脑的早期侮辱或伤害与许多人有关 衰弱的发育障碍，包括严重学习 残疾和智力低下。许多的共同特征 这些疾病是大脑皮层的异常形态发生。 临床观察者长期以来假定皮质异常 细胞形态学负责行为变化和 发育性脑部疾病的认知缺陷。但是，很少 已经尝试了实验检验该假设的尝试。 在这里，我们利用鼠标模型来解决以下假设 皮质细胞形态异常可能与受损 认知行为。在小鼠中，胆碱能预测 核心核面积[NBM]出生时入侵新皮层 在时间和空间上非常适合在 形态发生。当出生时在NBM区域进行病变时， 随之而来的皮质胆碱能标记物的短暂耗竭 伴随着智障神经元成熟。皮质 细胞结构和连通性仍在永久性地变为 成年后，尽管新皮层的胆碱能重新加剧。最近的 接受双侧NBM的小鼠的行为实验 出生时的病变显示记忆和学习中的缺陷 成年动物。初步结果表明这些 行为缺陷与特定的形态学和 脑皮质中的神经化学特征。 该项目旨在l）检查和量化密钥 皮质中的形态和神经化学特征 NBM新生小鼠结束行为后的新生小鼠 成年初期的测试；这些数据将比被检查 与行为测试评分的相关性； 2）调查 新生儿病变后的皮质形态发生异常 小鼠中的NBM区域是选择性耗竭的结果 胆碱能传入纤维和/或神经传递和3） 培训少数民族学生的基本实验室和研究技能 通过参与生物医学相关的研究 项目