Gervasoni D, Darracq L, Fort P, Soulière F, Chouvet G, Luppi P H
Laboratoire de Médecine Expérimentale, INSERM U480, CNRS ERS 5645, Faculté de Pharmacie, Université Claude Bernard Lyon I, France.
Eur J Neurosci. 1998 Mar;10(3):964-70. doi: 10.1046/j.1460-9568.1998.00106.x.
It is well known that noradrenergic locus coeruleus (LC) neurons decrease their activity during slow wave sleep (SWS) and are virtually quiescent during paradoxical sleep (PS). It has been proposed that a GABAergic input could be directly responsible for this sleep-dependent neuronal inactivation. To test this hypothesis, we used a new method combining polygraphic recordings, microiontophoresis and single-unit extracellular recordings in unanaesthetized head-restrained rats. We found that iontophoretic application of bicuculline, a specific GABA(A)-receptor antagonist, during PS and SWS restore a tonic firing in the LC noradrenergic neurons. We further observed that the application of bicuculline during wakefulness (W) induced an increase of the discharge rate. Of particular importance for the interpretation of these results, using the microdialysis technique, Nitz and Siegel (Neuroscience, 1997; 78: 795) recently found an increase of the GABA release in the cat LC during SWS and PS as compared with waking values. Based on these and our results, we therefore propose that during W, the LC cells are under a GABAergic inhibitory tone which progressively increases at the entrance and during SWS and PS and is responsible for the inactivation of these neurons during these states.
众所周知，去甲肾上腺素能蓝斑（LC）神经元在慢波睡眠（SWS）期间活动减少，而在异相睡眠（PS）期间几乎静止。有人提出，γ-氨基丁酸能（GABAergic）输入可能直接导致这种依赖睡眠的神经元失活。为了验证这一假设，我们采用了一种新方法，结合了多导记录、微量离子电泳和在未麻醉的头部固定大鼠中的单单位细胞外记录。我们发现，在PS和SWS期间，通过离子电泳应用荷包牡丹碱（一种特异性GABA(A)受体拮抗剂）可恢复LC去甲肾上腺素能神经元的紧张性放电。我们进一步观察到，在清醒（W）期间应用荷包牡丹碱会导致放电率增加。对于解释这些结果特别重要的是，使用微透析技术，Nitz和Siegel（《神经科学》，1997年；78: 795）最近发现，与清醒时的值相比，在SWS和PS期间猫LC中的GABA释放增加。基于这些以及我们的结果，因此我们提出，在W期间，LC细胞处于GABA能抑制性张力之下，这种张力在进入睡眠、SWS和PS期间逐渐增加，并导致这些神经元在这些状态下失活。
