Somatostatin Interneurons Control a Key Component of Mismatch Negativity in Mouse Visual Cortex.
Somatostatin Interneurons Control a Key Component of Mismatch Negativity in Mouse Visual Cortex.
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DOI：
10.1016/j.celrep.2016.06.037
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发表时间：
2016-07-19
期刊：
影响因子：
8.8
通讯作者：
Yuste R
中科院分区：
文献类型：
--
作者：
Hamm JP;Yuste R
精神分裂症患者的感觉处理有缺陷，破坏了他们对变化的环境的感知和联系。这种损伤可以通过减少的“失配负性”指数（MMN）来捕捉，MMN是精神病的脑电图生物标志物。造成MMN的生物因素尚不清楚，尽管可以应用遗传和光学方法的小鼠研究已经提供了一些见解。通过对清醒小鼠的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（减少）反应，对异常刺激表现出放大反应，这是人类MMN的关键组成部分。此外，含有生长抑素的中间神经元的药物遗传沉默特异性地消除了这种放大及其相关的θ / α波段反应，使刺激特异性适应和相关的γ波段调节保持完整。我们的研究结果证实了MMN的小鼠模型，并表明含有生长抑素的中间神经元异常导致MMN和精神分裂症的感觉缺陷。
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” index (MMN), an electroencephalographic biomarker of psychosis. The biological factors contributing to MMN are unclear, though mouse research, where 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 i) adapted (decreased) responses to repeated stimuli and ii) 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.