3月31日,，美國哥倫比亞大學(xué)研究人員報告說，他們通過動物實驗發(fā)現(xiàn),，一種與精神分裂癥相關(guān)的遺傳缺陷會影響大腦海馬區(qū)和額前葉之間的信息交流,，它可能也是腦功能障礙的一個基礎(chǔ)性致病因素。
這種遺傳缺陷名為22號染色體長臂近端微片段缺失,，是人類最常見的遺傳缺陷之一,。此前研究已經(jīng)證實，人體多個器官的異常均歸因于這種缺陷,，攜帶這種缺陷的人患精神分裂癥風(fēng)險比常人高30倍,。
為研究這種缺陷對大腦回路的影響,，哥倫比亞大學(xué)研究人員培育了一批具有類似遺傳缺陷的轉(zhuǎn)基因?qū)嶒炇螅屗鼈兣c健康實驗鼠均參加一項記憶測試,，通過一個迷宮并原路返回的實驗鼠可以得到獎勵,。測試期間，研究人員記錄了它們的大腦活動,。
研究人員介紹說,，完成這項測試需要實驗鼠大腦海馬區(qū)和額前葉密切配合，海馬區(qū)是大腦負(fù)責(zé)學(xué)習(xí)和記憶的區(qū)域,，額前葉主要負(fù)責(zé)思考,、推理、決策以及執(zhí)行任務(wù)等高級認(rèn)知功能,。這兩個區(qū)域的神經(jīng)元活動越同步,，彼此之間的信息傳遞越佳，實驗鼠的表現(xiàn)也會越好,。測試結(jié)果顯示,，轉(zhuǎn)基因?qū)嶒炇蟠竽X海馬區(qū)和額前葉交流明顯存在障礙，它們的表現(xiàn)遠(yuǎn)遜于健康實驗鼠,。
這項研究成果4月1日發(fā)表在英國《自然》雜志網(wǎng)絡(luò)版上,。研究人員說，他們需要進(jìn)行更多研究以確認(rèn)這種缺陷是否會在人體中導(dǎo)致類似異常,。(生物谷Bioon.com)
生物谷推薦原文出處：
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.
