3月31日，美国哥伦比亚大学研究人员报告说，他们通过动物实验发现，一种与精神分裂症相关的遗传缺陷会影响大脑海马区和额前叶之间的信息交流，它可能也是脑功能障碍的一个基础性致病因素。
这种遗传缺陷名为22号染色体长臂近端微片段缺失，是人类最常见的遗传缺陷之一。此前研究已经证实，人体多个器官的异常均归因于这种缺陷，携带这种缺陷的人患精神分裂症风险比常人高30倍。
为研究这种缺陷对大脑回路的影响，哥伦比亚大学研究人员培育了一批具有类似遗传缺陷的转基因实验鼠，让它们与健康实验鼠均参加一项记忆测试，通过一个迷宫并原路返回的实验鼠可以得到奖励。测试期间，研究人员记录了它们的大脑活动。
研究人员介绍说，完成这项测试需要实验鼠大脑海马区和额前叶密切配合，海马区是大脑负责学习和记忆的区域，额前叶主要负责思考、推理、决策以及执行任务等高级认知功能。这两个区域的神经元活动越同步，彼此之间的信息传递越佳，实验鼠的表现也会越好。测试结果显示，转基因实验鼠大脑海马区和额前叶交流明显存在障碍，它们的表现远逊于健康实验鼠。
这项研究成果4月1日发表在英国《自然》杂志网络版上。研究人员说，他们需要进行更多研究以确认这种缺陷是否会在人体中导致类似异常。(生物谷Bioon.com)
生物谷推荐原文出处：
Nature doi:10.1038/nature08855
Impaired hippocampal–prefrontal synchrony in a genetic mouse model of schizophrenia
Torfi Sigurdsson1, Kimberly L. Stark1,2, Maria Karayiorgou1,4, Joseph A. Gogos2,3 & Joshua A. Gordon1,4
Department of Psychiatry,
Department of Physiology and Cellular Biophysics,
Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
New York State Psychiatric Institute, New York, New York 10032, USA
Abnormalities in functional connectivity between brain areas have been postulated as an important pathophysiological mechanism underlying schizophrenia1, 2. In particular, macroscopic measurements of brain activity in patients suggest that functional connectivity between the frontal and temporal lobes may be altered3, 4. However, it remains unclear whether such dysconnectivity relates to the aetiology of the illness, and how it is manifested in the activity of neural circuits. Because schizophrenia has a strong genetic component5, animal models of genetic risk factors are likely to aid our understanding of the pathogenesis and pathophysiology of the disease. Here we study Df(16)A +/– mice, which model a microdeletion on human chromosome 22 (22q11.2) that constitutes one of the largest known genetic risk factors for schizophrenia6. To examine functional connectivity in these mice, we measured the synchronization of neural activity between the hippocampus and the prefrontal cortex during the performance of a task requiring working memory, which is one of the cognitive functions disrupted in the disease. In wild-type mice, hippocampal–prefrontal synchrony increased during working memory performance, consistent with previous reports in rats7. Df(16)A +/– mice, which are impaired in the acquisition of the task, showed drastically reduced synchrony, measured both by phase-locking of prefrontal cells to hippocampal theta oscillations and by coherence of prefrontal and hippocampal local field potentials. Furthermore, the magnitude of hippocampal–prefrontal coherence at the onset of training could be used to predict the time it took the Df(16)A +/– mice to learn the task and increased more slowly during task acquisition. These data suggest how the deficits in functional connectivity observed in patients with schizophrenia may be realized at the single-neuron level. Our findings further suggest that impaired long-range synchrony of neural activity is one consequence of the 22q11.2 deletion and may be a fundamental component of the pathophysiology underlying schizophrenia.
