Adenosine inhibits the excitatory synaptic inputs to Basal forebrain cholinergic, GABAergic, and parvalbumin neurons in mice.
Adenosine inhibits the excitatory synaptic inputs to Basal forebrain cholinergic, GABAergic, and parvalbumin neurons in mice.
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DOI：
10.3389/fneur.2013.00077
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发表时间：
2013
影响因子：
3.4
通讯作者：
Brown RE
中科院分区：
文献类型：
--
作者：
Yang C;Franciosi S;Brown RE
咖啡和茶含有兴奋剂咖啡因和茶碱。这些化合物作为腺苷受体的拮抗剂。腺苷促进睡眠，其细胞外浓度升高与长时间的觉醒有关，特别是在参与激活大脑皮层的基底前脑（BF）区域。然而，腺苷对BF神经元，特别是非胆碱能神经元的作用还不完全清楚。在这里，我们使用全细胞膜片钳记录在小鼠脑切片制备两个验证的转基因小鼠系与荧光蛋白表达的GABA能或小清蛋白（PV）神经元，以确定腺苷的影响。从BF胆碱能神经元和BF GABA能神经元和PV神经元进行全细胞记录，其大小（>20 μm）和内在膜特性（突出的H电流）对应于皮质投射神经元。在我们记录的所有BF胆碱能神经元、GABA能神经元和PV神经元中，短暂（2分钟）应用腺苷（100 μM）浴降低了自发兴奋性突触后电流（EPSC）的频率，但不降低其振幅。此外，腺苷降低BF胆碱能神经元的微型EPSC的频率。腺苷对胆碱能神经元或GABA能神经元自发抑制性突触后电流的频率没有影响，但在一组GABA能神经元中，腺苷降低了H电流。腺苷的所有作用均被选择性腺苷A1受体拮抗剂环戊基茶碱（CPT，1 μM）阻断。腺苷无突触后效应。两者合计，我们的工作表明，腺苷促进睡眠的A1受体介导的抑制肾上腺素能输入皮质投射胆碱能和GABA/PV神经元。相反，咖啡因和茶碱通过抑制BF中的这些A1受体，从而促进注意力和认知所需的皮质中的高频振荡，来促进注意力觉醒。
Coffee and tea contain the stimulants caffeine and theophylline. These compounds act as antagonists of adenosine receptors. Adenosine promotes sleep and its extracellular concentration rises in association with prolonged wakefulness, particularly in the basal forebrain (BF) region involved in activating the cerebral cortex. However, the effect of adenosine on identified BF neurons, especially non-cholinergic neurons, is incompletely understood. Here we used whole-cell patch-clamp recordings in mouse brain slices prepared from two validated transgenic mouse lines with fluorescent proteins expressed in GABAergic or parvalbumin (PV) neurons to determine the effect of adenosine. Whole-cell recordings were made from BF cholinergic neurons and from BF GABAergic and PV neurons with the size (>20 μm) and intrinsic membrane properties (prominent H-currents) corresponding to cortically projecting neurons. A brief (2 min) bath application of adenosine (100 μM) decreased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) in all groups of BF cholinergic, GABAergic, and PV neurons we recorded. In addition, adenosine decreased the frequency of miniature EPSCs in BF cholinergic neurons. Adenosine had no effect on the frequency of spontaneous inhibitory postsynaptic currents in cholinergic neurons or GABAergic neurons with large H-currents but reduced them in a group of GABAergic neurons with smaller H-currents. All effects of adenosine were blocked by a selective, adenosine A1 receptor antagonist, cyclopentyltheophylline (CPT, 1 μM). Adenosine had no postsynaptic effects. Taken together, our work suggests that adenosine promotes sleep by an A1 receptor-mediated inhibition of glutamatergic inputs to cortically projecting cholinergic and GABA/PV neurons. Conversely, caffeine and theophylline promote attentive wakefulness by inhibiting these A1 receptors in BF thereby promoting the high-frequency oscillations in the cortex required for attention and cognition.
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影响因子：
3.7
作者：
Fredholm BB
通讯作者：
Fredholm BB
影响因子：
3.4
作者：
Berntson, GG;Shafi, R;Sarter, M
通讯作者：
Sarter, M
DOI：
10.1016/s0169-328x(99)00219-3
发表时间：
1999-11-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Basheer, R;Porkka-Heiskanen, T;McCarley, RW
通讯作者：
McCarley, RW
影响因子：
25
作者：
Huang, ZL;Qu, WM;Hayaishi, O
通讯作者：
Hayaishi, O
影响因子：
3.3
作者：
Arrigoni, E.;Chamberlin, N. L.;McCarley, R. W.
通讯作者：
McCarley, R. W.