“22q11.2微缺失（微刪除）”是精神分裂癥最可靠的已知遺傳風(fēng)險(xiǎn)因素之一,。相應(yīng)染色體區(qū)域有一處中斷的小鼠會(huì)有工作記憶問題，這是精神分裂癥 的一個(gè)特征,。
Sigurdsson等人發(fā)現(xiàn),，這些小鼠前額皮質(zhì)和海馬神經(jīng)元之間的同步激發(fā)也有中斷，這種同步激發(fā)是一個(gè)已被與學(xué)習(xí)和記憶聯(lián)系在一起的現(xiàn)象,，而且它在精神分裂癥患者中也受到破壞,。
這些發(fā)現(xiàn)表明，腦中這些區(qū)域之間溝通的破壞可能是精神分裂癥發(fā)病的深層原因,，而試圖修復(fù)這種破壞的工作可能會(huì)導(dǎo)致新療法的問世,。（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.
