Steenland Hendrik W, Liu Hattie, Horner Richard L
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
J Neurosci. 2008 Jul 2;28(27):6826-35. doi: 10.1523/JNEUROSCI.1019-08.2008.
The transmission of rhythmic drive to respiratory motoneurons in vitro is critically dependent on glutamate acting primarily on non-NMDA receptors. We determined whether both non-NMDA and NMDA receptors contribute to respiratory drive transmission at respiratory motoneurons in the intact organism, both in the state of anesthesia and in the same animals during natural behaviors. Twenty-seven rats were implanted with electroencephalogram and neck electrodes to record sleep-wake states and genioglossus and diaphragm electrodes for respiratory muscle recordings. Microdialysis probes were inserted into the hypoglossal motor nucleus (HMN). Under anesthesia, non-NMDA or NMDA receptor antagonism significantly decreased respiratory-related genioglossus activity, indicating a contribution of each receptor to respiratory drive transmission at the HMN. However, despite the presence of respiratory-related genioglossus activity in the same rats across sleep-wake states, neither non-NMDA receptor antagonism at the HMN nor glutamate uptake inhibition had any effect on respiratory-related genioglossus activity. These results showed that, compared with anesthesia, respiratory drive transmission through the non-NMDA receptor is low in the behaving organism. In contrast, glutamate uptake inhibition increased tonic genioglossus activity in wakefulness and non-rapid-eye-movement sleep, indicating a functional endogenous glutamatergic modulation of tonic, but not respiratory, motor tone. Such an effect on tonic drive may contribute to the suppression of both tonic and respiratory-related genioglossus activity in wakefulness and sleep with NMDA receptor antagonism at the HMN. These data do not refute previous identification of a glutamatergic (mostly non-NMDA receptor activating) respiratory drive to hypoglossal motoneurons, but this mechanism is more prominent in anesthetized or in vitro preparations.
体外向呼吸运动神经元传递节律性驱动主要依赖于谷氨酸作用于非NMDA受体。我们确定了在完整机体中，无论是在麻醉状态还是在自然行为期间的同一只动物中，非NMDA和NMDA受体是否都对呼吸运动神经元的呼吸驱动传递有作用。27只大鼠植入了脑电图和颈部电极以记录睡眠-觉醒状态，以及颏舌肌和膈肌电极以记录呼吸肌活动。将微透析探针插入舌下运动核（HMN）。在麻醉状态下，非NMDA或NMDA受体拮抗作用显著降低了与呼吸相关的颏舌肌活动，表明每种受体都对HMN处的呼吸驱动传递有作用。然而，尽管在不同睡眠-觉醒状态下的同一只大鼠中存在与呼吸相关的颏舌肌活动，但HMN处的非NMDA受体拮抗作用或谷氨酸摄取抑制对与呼吸相关的颏舌肌活动均无任何影响。这些结果表明，与麻醉状态相比，在行为机体中通过非NMDA受体的呼吸驱动传递较低。相反，谷氨酸摄取抑制增加了清醒和非快速眼动睡眠时的紧张性颏舌肌活动，表明存在对紧张性而非呼吸性运动张力的功能性内源性谷氨酸能调节。这种对紧张性驱动的作用可能有助于在HMN处使用NMDA受体拮抗剂时抑制清醒和睡眠时的紧张性及与呼吸相关的颏舌肌活动。这些数据并不反驳先前确定的向舌下运动神经元的谷氨酸能（主要是激活非NMDA受体）呼吸驱动，但这种机制在麻醉或体外制备中更为突出。
