Hamm Jordan P, Yuste Rafael
Neurotechnology Center and Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Neurotechnology Center and Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Cell Rep. 2016 Jul 19;16(3):597-604. doi: 10.1016/j.celrep.2016.06.037. Epub 2016 Jul 7.
Patients with schizophrenia have deficient sensory processing, undermining how they perceive and relate to a changing environment. This impairment can be captured by the reduced mismatch negativity (MMN) index, an electroencephalographic biomarker of psychosis. The biological factors contributing to MMN are unclear, though mouse research, in which genetic and optical methods could be applied, has given some insight. Using fast two-photon calcium imaging and multielectrode recordings in awake mice, we find that visual cortical circuits display adapted (decreased) responses to repeated stimuli and amplified responses to a deviant stimulus, the key component of human MMN. Moreover, pharmacogenetic silencing of somatostatin-containing interneurons specifically eliminated this amplification, along with its associated theta/alpha-band response, leaving stimulus-specific adaption and related gamma-band modulations intact. Our results validate a mouse model of MMN and suggest that abnormalities in somatostatin-containing interneurons cause sensory deficits underlying MMN and schizophrenia.
精神分裂症患者存在感觉加工缺陷，这会损害他们对不断变化的环境的感知及与之建立联系的能力。这种损害可以通过降低的失匹配负波（MMN）指数来体现，MMN是一种精神病的脑电图生物标志物。尽管小鼠研究（其中可以应用基因和光学方法）已经提供了一些见解，但导致MMN的生物学因素仍不清楚。通过在清醒小鼠中使用快速双光子钙成像和多电极记录，我们发现视觉皮层回路对重复刺激表现出适应性（降低）反应，而对偏差刺激表现出放大反应，这是人类MMN的关键组成部分。此外，对含生长抑素中间神经元的药物遗传学沉默特异性地消除了这种放大反应及其相关的theta/alpha波段反应，而刺激特异性适应和相关的gamma波段调制则保持完整。我们的结果验证了MMN的小鼠模型，并表明含生长抑素中间神经元的异常导致了MMN和精神分裂症潜在的感觉缺陷。
