Adenosine inhibits basal forebrain cholinergic and noncholinergic neurons in vitro
Adenosine inhibits basal forebrain cholinergic and noncholinergic neurons in vitro
复制标题
DOI：
10.1016/j.neuroscience.2006.02.010
复制
发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
McCarley, R. W.
中科院分区：
文献类型：
--
作者：
Arrigoni, E.;Chamberlin, N. L.;McCarley, R. W.
腺苷被认为是一种动态平衡的“睡眠因子”，通过影响几个睡眠-觉醒调节系统来促进从清醒到睡眠的转变。在基底前脑，腺苷在清醒时积聚，当局部应用时，会抑制神经元活动，促进睡眠。然而，介导这些效应的神经元表型尚不清楚。我们在大鼠脑片上采用全细胞膜片钳记录技术，研究了腺苷对大细胞视前核和无名核胆碱能和非胆碱能神经元的影响。腺苷(0.5-100mM)通过激活内向整流钾电流降低大细胞视前核和无名质胆碱能神经元的放电频率，该电流在-82 mV时反转，并被钡(100mM)阻断。应用A型受体拮抗剂8-环-戊基-茶碱(200 NM)阻断腺苷的作用。腺苷还在两组电生理上不同的非胆碱能大细胞视前核和无名质神经元上进行了测试。在第一组中，腺苷通过激活突触后A受体，通过抑制超极化激活的阳离子电流来减少自发放电。用ZD7288(20mM)阻断H-电流，可消除腺苷对这些神经元的作用。第二组不受腺苷的影响。这些结果表明，在基底前脑的大细胞视前核和无名质区，腺苷既抑制胆碱能神经元，又抑制非胆碱能神经元的亚群。这两种作用都是通过突触后受体发生的，但通过两种不同的机制在下游进行调节。(C)2006年IBRO。爱思唯尔有限公司出版。保留所有权利。
Adenosine has been proposed as a homeostatic "sleep factor" that promotes the transition from waking to sleep by affecting several sleep-wake regulatory systems. In the basal forebrain, adenosine accumulates during wakefulness and, when locally applied, suppresses neuronal activity and promotes sleep. However, the neuronal phenotype mediating these effects is unknown. We used whole-cell patch-clamp recordings in in vitro rat brain slices to investigate the effect of adenosine on identified cholinergic and noncholinergic neurons of the magnocellular preoptic nucleus and substantia innominata. Adenosine (0.5-100 mu M) reduced the magnocellular preoptic nucleus and substantia innominata cholinergic neuronal firing rate by activating an inwardly rectifying potassium current that reversed at -82 mV and was blocked by barium (100 mu M). Application of the A, receptor antagonist 8-cyclo-pentyl-theophylline (200 nM) blocked the effects of adenosine. Adenosine was also tested on two groups of electrophysiologically distinct noncholinergic magnocellular preoptic nucleus and substantia innominata neurons. In the first group adenosine, via activation of postsynaptic A, receptors, reduced spontaneous firing via inhibition of the hyperpolarization-activated cation current. Blocking the H-current with ZD7288 (20 mu M) abolished adenosine effects on these neurons. The second group was not affected by adenosine. These results demonstrate that, in the magnocellular preoptic nucleus and substantia innominata region of the basal forebrain, adenosine inhibits both cholinergic neurons and a subset of noncholinergic neurons. Both of these effects occur via postsynaptic A, receptors, but are mediated downstream by two separate mechanisms. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.