High-frequency neuronal population oscillations (HFO, 130-180 Hz) are robustly potentiated by subanesthetic doses of ketamine. This frequency band has been recorded in functionally and neuroanatomically diverse cortical and subcortical regions, notably ventral striatal areas. However, the locus of generation remains largely unknown. There is compelling evidence that olfactory regions can drive oscillations in distant areas. Here we tested the hypothesis that the olfactory bulb (OB) is a locus for the generation of HFO following a subanesthetic dose of ketamine. The effect of ketamine on the electrophysiological activity of the OB and ventral striatum of male Wistar rats was examined using field potential and unit recordings, local inhibition, naris blockade, current source density and causality estimates. Ketamine-HFO was of larger magnitude and was phase-advanced in the OB relative to ventral striatum. Granger causality analysis was consistent with the OB as the source of HFO. Unilateral local inhibition of the OB and naris blockade both attenuated HFO recorded locally and in the ventral striatum. Within the OB, current source density analysis revealed HFO current dipoles close to the mitral layer and unit firing of mitral/tufted cells was phase locked to HFO. Our results reveal the OB as a source of ketamine-HFO which can contribute to HFO in the ventral striatum, known to project diffusely to many other brain regions. These findings provide a new conceptual understanding on how changes in olfactory system function may have implications for neurological disorders involving NMDA receptor dysfunction such as schizophrenia and depression.

中文翻译：

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啮齿动物的嗅球是与亚麻醉剂量的氯胺酮相关的高频振荡（130-180 Hz）的来源。


亚麻醉剂量的氯胺酮会强烈增强高频神经元群体振荡（HFO，130-180 Hz）。该频段已被记录在功能和神经解剖学上不同的皮质和皮质下区域，特别是腹侧纹状体区域。然而，生成轨迹仍然很大程度上未知。有令人信服的证据表明嗅觉区域可以驱动远处区域的振荡。在这里，我们测试了以下假设：嗅球 (OB) 是亚麻醉剂量氯胺酮后产生 HFO 的场所。使用场电位和单位记录、局部抑制、鼻孔阻滞、电流源密度和因果关系估计来检查氯胺酮对雄性 Wistar 大鼠 OB 和腹侧纹状体电生理活动的影响。相对于腹侧纹状体，Ketamine-HFO 在 OB 中的幅度更大并且相位超前。格兰杰因果分析与 OB 作为 HFO 来源一致。 OB 的单侧局部抑制和鼻孔阻滞均减弱了局部和腹侧纹状体记录的 HFO。在 OB 内，电流源密度分析显示 HFO 电流偶极子靠近二尖瓣层，并且二尖瓣/簇状细胞的单位放电被锁相至 HFO。我们的研究结果表明，OB是氯胺酮-HFO的来源，它可以在腹侧纹状体中产生HFO，已知其会扩散到许多其他大脑区域。这些发现为嗅觉系统功能的变化如何影响涉及 NMDA 受体功能障碍的神经系统疾病（例如精神分裂症和抑郁症）提供了新的概念性理解。