“22q11.2微缺失（微删除）”是精神分裂症最可靠的已知遗传风险因素之一。相应染色体区域有一处中断的小鼠会有工作记忆问题，这是精神分裂症 的一个特征。
Sigurdsson等人发现，这些小鼠前额皮质和海马神经元之间的同步激发也有中断，这种同步激发是一个已被与学习和记忆联系在一起的现象，而且它在精神分裂症患者中也受到破坏。
这些发现表明，脑中这些区域之间沟通的破坏可能是精神分裂症发病的深层原因，而试图修复这种破坏的工作可能会导致新疗法的问世。（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.
