Adenosine inhibits glutamatergic input to basal forebrain cholinergic neurons
Adenosine inhibits glutamatergic input to basal forebrain cholinergic neurons
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DOI：
10.1152/jn.00528.2011
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发表时间：
2012-05-01
影响因子：
2.5
通讯作者：
Arrigoni, E.
中科院分区：
文献类型：
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作者：
Hawryluk, J. M.;Ferrari, L. L.;Arrigoni, E.
Hawryluk JM、Ferrari LL、Keating SA、Arrigoni E。腺苷抑制基底前脑胆碱能神经元的谷氨酸输入。 J Neurophysiol 107: 2769-2781, 2012。首次发表于 2012 年 2 月 22 日； doi:10.1152/jn.00528.2011.-腺苷已被提议作为一种内源性稳态睡眠因子，在清醒时积累并抑制唤醒活跃神经元以促进睡眠。据具体假设，腺苷通过直接抑制基底前脑 (BF) 的唤醒活性神经元，特别是 BF 胆碱能神经元，来降低觉醒度并促进睡眠恢复。我们之前证明腺苷直接抑制 BF 胆碱能神经元。在这里，我们研究了 1) 腺苷如何调节 BF 胆碱能神经元的谷氨酸输入，以及 2) 腺苷摄取和腺苷代谢如何参与调节细胞外腺苷水平。我们的实验是使用小鼠脑切片的全细胞膜片钳记录进行的。我们发现，在 BF 胆碱能神经元中，腺苷降低了 AMPA 介导的诱发谷氨酸能兴奋性突触后电流 (EP-SC) 的幅度，并通过突触前 A(1) 受体降低了自发和微型 EPSC 的频率。因此，我们已经证明，除了直接抑制 BF 胆碱能神经元外，腺苷还能抑制这些神经元的兴奋性输入。因此，直接和间接抑制可能协同促进 BF 中腺苷的睡眠促进作用。我们还发现，阻断腺苷通过平衡核苷转运蛋白的流入或抑制腺苷激酶和腺苷脱氨酶会增加内源性腺苷抑制张力，这表明调节基底前脑细胞外腺苷水平的可能机制。
Hawryluk JM, Ferrari LL, Keating SA, Arrigoni E. Adenosine inhibits glutamatergic input to basal forebrain cholinergic neurons. J Neurophysiol 107: 2769-2781, 2012. First published February 22, 2012; doi:10.1152/jn.00528.2011.-Adenosine has been proposed as an endogenous homeostatic sleep factor that accumulates during waking and inhibits wake-active neurons to promote sleep. It has been specifically hypothesized that adenosine decreases wakefulness and promotes sleep recovery by directly inhibiting wake-active neurons of the basal forebrain (BF), particularly BF cholinergic neurons. We previously showed that adenosine directly inhibits BF cholinergic neurons. Here, we investigated 1) how adenosine modulates glutamatergic input to BF cholinergic neurons and 2) how adenosine uptake and adenosine metabolism are involved in regulating extracellular levels of adenosine. Our experiments were conducted using whole cell patch-clamp recordings in mouse brain slices. We found that in BF cholinergic neurons, adenosine reduced the amplitude of AMPA-mediated evoked glutamatergic excitatory postsynaptic currents (EP-SCs) and decreased the frequency of spontaneous and miniature EPSCs through presynaptic A(1) receptors. Thus we have demonstrated that in addition to directly inhibiting BF cholinergic neurons, adenosine depresses excitatory inputs to these neurons. It is therefore possible that both direct and indirect inhibition may synergistically contribute to the sleep-promoting effects of adenosine in the BF. We also found that blocking the influx of adenosine through the equilibrative nucleoside transporters or inhibiting adenosine kinase and adenosine deaminase increased endogenous adenosine inhibitory tone, suggesting a possible mechanism through which adenosine extracellular levels in the basal forebrain are regulated.