Role of Somatostatin-Positive Cortical Interneurons in the Generation of Sleep Slow Waves
Role of Somatostatin-Positive Cortical Interneurons in the Generation of Sleep Slow Waves
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DOI：
10.1523/jneurosci.1303-17.2017
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发表时间：
2017-09-20
影响因子：
5.3
通讯作者：
Tononi, Giulio
中科院分区：
文献类型：
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作者：
Funk, Chadd M.;Peelman, Kayla;Tononi, Giulio
在非快速眼动（NREM）睡眠期间，皮质和丘脑神经元每隔一秒左右在ON期和OFF期之间振荡，ON期以膜去极化和唤醒样紧张性放电为特征，OFF期以膜超极化和神经元沉默为特征。皮层慢波是NREM睡眠的标志，反映了皮层神经元中接近同步的OFF期。然而，触发这种OFF期的机制尚不清楚，因为几乎没有体细胞抑制的证据。我们研究了表达生长抑素（SOM）的皮质抑制性中间神经元，因为它们中的70%类似于Martinotti细胞，其靶向弥漫性第I层，并且可以在突触前、突触能末梢和突触后、顶端树突阻断兴奋性传递，而不抑制索马。在自由移动的雄性小鼠中，我们发现SOM +细胞可以在慢波之前立即发射，并且在NREM睡眠的ON期间它们的光遗传学刺激触发长的OFF期。接下来，我们发现SOM +细胞的化学发生激活增加慢波活动（SWA），个别慢波的斜率，和NREM睡眠持续时间;而它们的化学发生抑制减少SWA和慢波发生率，而不改变NREM睡眠中花费的时间。相比之下，激活小清蛋白+（PV+）细胞，数量最多的群体皮层抑制性神经元，大大减少SWA和皮层放电，触发短OFF期NREM睡眠，并增加NREM睡眠持续时间。因此，SOM +细胞，而不是PV +细胞，参与睡眠慢波的产生。Martinotti细胞是否单独负责这种效应，或者由其他类型的抑制性神经元补充，仍有待研究。
During non-rapid eye-movement (NREM) sleep, cortical and thalamic neurons oscillate every second or so between ON periods, characterized by membrane depolarization and wake-like tonic firing, and OFF periods, characterized by membrane hyperpolarization and neuronal silence. Cortical slow waves, the hallmark of NREM sleep, reflect near-synchronous OFF periods in cortical neurons. However, the mechanisms triggering such OFF periods are unclear, as there is little evidence for somatic inhibition. We studied cortical inhibitory interneurons that express somatostatin (SOM), because similar to 70% of them are Martinotti cells that target diffusely layer I and can block excitatory transmission presynaptically, at glutamatergic terminals, and postsynaptically, at apical dendrites, without inhibiting the soma. In freely moving male mice, we show that SOM + cells can fire immediately before slow waves and their optogenetic stimulation during ON periods of NREM sleep triggers long OFF periods. Next, we show that chemogenetic activation of SOM + cells increases slow-wave activity (SWA), slope of individual slow waves, and NREM sleep duration; whereas their chemogenetic inhibition decreases SWA and slow-wave incidence without changing time spent in NREM sleep. By contrast, activation of parvalbumin + (PV+) cells, the most numerous population of cortical inhibitory neurons, greatly decreases SWA and cortical firing, triggers short OFF periods in NREM sleep, and increases NREM sleep duration. Thus SOM + cells, but not PV + cells, are involved in the generation of sleep slow waves. Whether Martinotti cells are solely responsible for this effect, or are complemented by other classes of inhibitory neurons, remains to be investigated.