Seigneur Josée, Kroeger Daniel, Nita Dragos A, Amzica Florin
Laboratoire de neurophysiologie, Faculté de médecine, Université Laval, Quebec, Canada G1K 7P4.
Cereb Cortex. 2006 May;16(5):655-68. doi: 10.1093/cercor/bhj011. Epub 2005 Aug 10.
This study aims at understanding complex interactions between cortical neurons, glia and blood supply developing during the transition from slow-wave sleep to wakefulness. In spite of essential advances from in vitro and culture preparations, the basic mechanisms of glial interactions with their cellular and ionic environment had remained uninvestigated in vivo. Here we approach this issue by performing simultaneous intracellular recordings of cortical neurons and glia, together with measurements of cerebral blood flow (CBF), extracellular K+ concentrations and local field potentials in both anesthetized (ketamine-xylazine) and naturally behaving cats. Under anesthesia, cortical activation was elicited with electric stimulation of cholinergic nuclei (pedunculopontine tegmental in the brainstem and/or nucleus basalis in the basal forebrain). Iontophoretic application of acetylcholine on the recorded cells was also used. In the vast majority of cases (> 80%) glial cells were hyperpolarized during electric stimulation or spontaneous activation. This result was also obtained in all cases where iontophoresis was used or when glutamatergic kainate/quisqualate receptors were blocked with 6-cyano-7-nitroquinoxaline-2,3-dione. The glial hyperpolarization was associated with steady neuronal depolarization, increased CBF, lower extracellular K+ concentration, increased membrane resistance, decreased membrane capacitance and persistent positive DC field potentials. In some cases of cortical activation (< 20%), glial cells displayed sustained depolarizing potentials, in parallel with neuronal depolarization, decreased CBF and more negative DC field potentials. The above-mentioned effects of cholinergic activation were blocked by the muscarinic antagonist scopolamine. We propose that the glial response to cholinergic activation results from the balance between the direct hyperpolarizing action of acetylcholine and the depolarizing modulation of glutamate from the neighboring neurons, in addition to the modulation of the interglial communication pathway and/or the ionic traffic across blood vessels.
本研究旨在了解在从慢波睡眠向清醒状态转变过程中，皮质神经元、神经胶质细胞和血液供应之间复杂的相互作用。尽管体外和培养制剂取得了重要进展，但神经胶质细胞与其细胞及离子环境相互作用的基本机制在体内仍未得到研究。在此，我们通过在麻醉（氯胺酮-赛拉嗪）和自然行为的猫中，同时对皮质神经元和神经胶质细胞进行细胞内记录，并测量脑血流量（CBF）、细胞外钾离子浓度和局部场电位，来解决这个问题。在麻醉状态下，通过电刺激胆碱能核团（脑干中的脚桥被盖核和/或基底前脑的基底核）引发皮质激活。还使用了向记录细胞上离子导入乙酰胆碱的方法。在绝大多数情况下（>80%），神经胶质细胞在电刺激或自发激活期间发生超极化。在用离子导入法的所有情况下，或在用6-氰基-7-硝基喹喔啉-2,3-二酮阻断谷氨酸能海人藻酸/quisqualate受体时，也得到了这一结果。神经胶质细胞超极化与神经元稳定去极化、CBF增加、细胞外钾离子浓度降低、膜电阻增加、膜电容降低以及持续的正直流场电位有关。在某些皮质激活的情况下（<20%），神经胶质细胞表现出持续的去极化电位，同时伴有神经元去极化、CBF降低和更负的直流场电位。胆碱能激活的上述效应被毒蕈碱拮抗剂东莨菪碱阻断。我们提出，神经胶质细胞对胆碱能激活的反应是由乙酰胆碱的直接超极化作用与来自相邻神经元的谷氨酸去极化调节之间的平衡所致，此外还涉及神经胶质细胞间通讯途径的调节和/或跨血管的离子运输调节。
