ABNORMAL ONTOGENY AND CORTICAL FUNCTION IN A MOUSE MODEL

早期对大脑的侮辱或伤害涉及许多 衰弱性发育障碍，包括严重的学习障碍 残疾和智力迟钝。一个共同的特点，许多 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一直认为， 细胞形态学负责行为变化， 大脑发育障碍中的认知缺陷但很少 已经尝试通过实验来检验该假设。 在这里，我们利用小鼠模型来解决假设， 异常的皮质细胞形态学可能与受损 认知行为在小鼠中，来自大脑皮层的胆碱能投射 基底核区[nBM]在出生时侵入新皮层， 在时间和空间上非常适合在以下方面发挥调节作用： 形态发生当在出生时在nBM区域进行损伤时， 皮质胆碱能标记物的短暂消耗， 伴随着神经元发育迟缓皮质 细胞结构和连接性仍然永久改变， 成年后，尽管胆碱能神经支配的新皮层。最近 接受双侧nBM的小鼠的行为实验 出生时的损伤显示这些人的记忆和学习能力不足， 成年后的动物初步结果表明，这些 行为缺陷与特定的形态和 大脑皮层的神经化学特征。 该项目旨在l）检查和量化关键 大脑皮层的形态学和神经化学特征 nBM损伤小鼠在完成行为学实验后， 在成年早期进行测试;这些数据将被检查， 与行为测试分数的相关性; 2）调查 新生儿损伤后的异常皮质形态发生 对小鼠nBM区的影响是选择性消耗 胆碱能传入纤维和/或神经传递，以及3） 培养少数民族学生基本的实验室和研究技能 通过他们参与一项生物医学相关研究， 项目

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