Nitrous oxide (N2O; laughing gas) has recently been reported as a putative rapid-acting antidepressant, but little is known about the underlying mechanisms. We performed transcriptomics, in situ hybridization, and electrophysiological studies to examine the potential shared signatures induced by 1 h inhalation of 50% N2O and a single subanesthetic dose of ketamine in the medial prefrontal cortex (mPFC) in adult mice. Both treatments similarly affected the transcription of several negative regulators of mitogen-activated protein kinases (MAPKs), namely, dual specificity phosphatases. The effects were primarily located in the pyramidal cells. Notably, the overall effects of N2O on mRNA expression were much more prominent and widespread compared to ketamine. Ketamine caused an elevation of the spiking frequency of putative pyramidal neurons and increased gamma activity (30-100 Hz) of cortical local field potentials. However, N2O produced no such effects. Spiking amplitudes and spike-to-local field potential phase locking of putative pyramidal neurons and interneurons in this brain area showed no uniform changes across treatments. Thus, this study characterized the electrophysiological and transcriptome-wide changes in mPFC triggered by exposure to N2O and compared them with those caused by the rapid-acting antidepressant ketamine in terms of both the direction of their regulation and localization.

中文翻译：

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一氧化二氮和氯胺酮对小鼠前额皮质的影响：比较研究

一氧化二氮（N2O；笑气）最近被报道为一种假定的速效抗抑郁药，但对其潜在机制知之甚少。我们进行了转录组学、原位杂交和电生理学研究，以检查成年小鼠内侧前额皮质 (mPFC) 吸入 1 小时 50% N2O 和单次亚麻醉剂量的氯胺酮诱导的潜在共同特征。两种处理类似地影响丝裂原激活蛋白激酶（MAPK）的几种负调节因子（即双特异性磷酸酶）的转录。影响主要位于锥体细胞。值得注意的是，与氯胺酮相比，N2O 对 mRNA 表达的总体影响更为突出和广泛。氯胺酮导致假定的锥体神经元的尖峰频率升高，并增加皮质局部场电位的伽马活性（30-100 Hz）。然而，N2O 却没有产生这样的效果。该大脑区域中假定的锥体神经元和中间神经元的尖峰振幅和尖峰至局部场电位锁相在治疗过程中没有表现出统一的变化。因此，本研究描述了暴露于 N2O 所引发的 mPFC 的电生理学和转录组变化，并将其与速效抗抑郁药氯胺酮引起的变化在调节方向和定位方面进行了比较。该大脑区域中假定的锥体神经元和中间神经元的尖峰振幅和尖峰至局部场电位锁相在治疗过程中没有表现出统一的变化。因此，本研究描述了暴露于 N2O 所引发的 mPFC 的电生理学和转录组变化，并将其与速效抗抑郁药氯胺酮引起的变化在调节方向和定位方面进行了比较。该大脑区域中假定的锥体神经元和中间神经元的尖峰振幅和尖峰至局部场电位锁相在治疗过程中没有表现出统一的变化。因此，本研究描述了暴露于 N2O 所引发的 mPFC 的电生理学和转录组变化，并将其与速效抗抑郁药氯胺酮引起的变化在调节方向和定位方面进行了比较。