Windels François, Kiyatkin Eugene A
Cellular Neurobiology Branch, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, DHHS, 333 Cassell Drive, Baltimore, MD 21224, USA.
Brain Res. 2006 May 1;1086(1):104-16. doi: 10.1016/j.brainres.2006.02.064. Epub 2006 Apr 5.
Although it is evident that general anesthesia should affect impulse activity and neurochemical responses of central neurons, there are limited studies in which these parameters were compared in both awake and anesthetized animal preparations. We used single-unit recording coupled with iontophoresis to examine impulse activity and responses of substantia nigra pars reticulata (SNr) neurons to GABA, glutamate (GLU), and dopamine (DA) in rats in awake, unrestrained conditions and during chloral hydrate anesthesia. SNr neurons in both conditions had similar organization of impulse flow, but during anesthesia, they have lower mean rates and discharge variability than in awake conditions. In individual units, discharge rate in awake, quietly resting rats was almost three-fold more variable than during anesthesia. These cells in both conditions were highly sensitive to iontophoretic GABA, but the response was stronger during anesthesia. In contrast to virtually no responses to GLU in awake conditions, most SNr neurons during anesthesia were excited by GLU; the response occurred preferentially in slow-firing units, which were atypical of awake conditions. Consistent with no postsynaptic DA receptors on SNr neurons, iontophoretic DA was ineffective in altering discharge rates in awake conditions, but often induced weak excitations during anesthesia. Although SNr neurons are autoactive, generating discharges without any excitatory input (i.e., in vitro), their impulse activity and responses to natural neurochemical inputs are strongly affected by general anesthesia. Some alterations appear to be specific to the general anesthetic used, while others probably reflect changes in the activity of afferent inputs, brain metabolism and neurotransmitter uptake that are typical to any type of general anesthesia. Therefore, an awake, freely moving animal preparation appears to be advantageous for studying impulse activity and neurochemical interactions at single-neuron level during physiologically relevant conditions.
尽管全身麻醉显然会影响中枢神经元的冲动活动和神经化学反应，但在清醒和麻醉动物制剂中比较这些参数的研究有限。我们使用单单位记录结合离子电泳来检查清醒、不受约束的大鼠以及水合氯醛麻醉期间黑质网状部（SNr）神经元对γ-氨基丁酸（GABA）、谷氨酸（GLU）和多巴胺（DA）的冲动活动和反应。在这两种情况下，SNr神经元的冲动流组织相似，但在麻醉期间，它们的平均发放率和放电变异性低于清醒状态。在单个单位中，清醒、安静休息的大鼠的放电率变异性几乎是麻醉期间的三倍。这两种情况下的这些细胞对离子电泳的GABA高度敏感，但麻醉期间的反应更强。与清醒状态下对GLU几乎无反应相反，大多数SNr神经元在麻醉期间被GLU兴奋；反应优先发生在发放缓慢的单位，这在清醒状态下不典型。与SNr神经元上无突触后DA受体一致，离子电泳的DA在清醒状态下改变放电率无效，但在麻醉期间常诱发微弱兴奋。尽管SNr神经元具有自发放电能力，即在没有任何兴奋性输入的情况下（即体外）产生放电，但其冲动活动和对天然神经化学输入的反应受到全身麻醉的强烈影响。一些改变似乎特定于所用的全身麻醉剂，而其他改变可能反映了任何类型全身麻醉典型的传入输入活动、脑代谢和神经递质摄取的变化。因此，清醒、自由活动的动物制剂似乎有利于在生理相关条件下研究单神经元水平的冲动活动和神经化学相互作用。
