Cortical nNOS neurons co-express the NK1 receptor and are depolarized by Substance P in multiple mammalian species
Cortical nNOS neurons co-express the NK1 receptor and are depolarized by Substance P in multiple mammalian species
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DOI：
10.3389/fncir.2012.00031
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发表时间：
2012-06-05
影响因子：
3.5
通讯作者：
Kilduff, Thomas S.
中科院分区：
文献类型：
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作者：
Dittrich, Lars;Heiss, Jaime E.;Kilduff, Thomas S.
我们之前已经证明，表达 I 型神经元一氧化氮合酶 (nNOS) 的神经元在小鼠、大鼠和仓鼠的皮层中具有睡眠活性。这些神经元具有 GABA 能，表达神经肽 Y (NPY)，并且在大鼠中共同表达 P 物质 (SP) 受体 NK1，这表明 SP 在睡眠/觉醒调节中可能发挥作用。为了评估哺乳动物皮质中 nNOS 和 NK1 的共表达程度，我们使用了 nNOS 和 NK1 的双重免疫荧光，并确定了小鼠、大鼠和松鼠猴皮质中的解剖分布。尽管皮层内的解剖分布具有物种特异性，但 I 型 nNOS 神经元在所有三个物种中共同表达 NK1。然后，我们使用 SP 缀合物四甲基罗丹明-SP (TMR-SP) 对小鼠和大鼠皮层神经元切片进行体外膜片钳记录，以识别 NK1 表达细胞，并评估 SP 对这些神经元的影响。 SP（0.03-1μM）的浴应用导致这些神经元的放电率持续增加；在河豚毒素存在下，去极化持续存在。这些结果表明 SP 在调节哺乳动物皮质睡眠活跃神经元中的保守作用。
We have previously demonstrated that Type I neuronal nitric oxide synthase (nNOS)-expressing neurons are sleep-active in the cortex of mice, rats, and hamsters. These neurons are known to the GABAergic, to express Neuropeptide Y (NPY) and, in rats, to co-express the Substance P (SP) receptor NK1, suggesting a possible role for SP in sleep/wake regulation. To evaluate the degree of co-expression of nNOS and NK1 in the cortex among mammals, we used double immunofluorescence for nNOS and NK1 and determined the anatomical distribution in mouse, rat, and squirrel monkey cortex. Type I nNOS neurons co-expressed NK1 in all three species although the anatomical distribution within the cortex was species-specific. We then performed in vitro patch clamp recordings in cortical neurons in mouse and rat slices using the SP conjugate tetramethylrhodamine-SP (TMR-SP) to identify NK1-expressing cells and evaluated the effects of SP on these neurons. Bath application of SP (0.03-1 mu M) resulted in a sustained increase in firing rate of these neurons; depolarization persisted in the presence of tetrodotoxin. These results suggest a conserved role for SP in the regulation of cortical sleep-active neurons in mammals.