Adenosine and sleep homeostasis in the basal forebrain
Adenosine and sleep homeostasis in the basal forebrain
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DOI：
10.1523/jneurosci.2181-06.2006
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发表时间：
2006-08-02
影响因子：
5.3
通讯作者：
Shiromani, Priyattam J.
中科院分区：
文献类型：
--
作者：
Blanco-Centurion, Carlos;Xu, Man;Shiromani, Priyattam J.
目前假设，睡眠的驱动力是由基底前脑（BF）胆碱能神经元的活性决定的，这些神经元释放腺苷（AD），这可能是因为在清醒期间与神经元放电相关的代谢活动增加，并且累积的AD开始抑制这些神经元，使得睡眠活跃的神经元可以变得活跃。这一假设来自于观察到AD诱导睡眠，并且基底前脑中AD水平随着觉醒而增加，但令人惊讶的是，它仍然没有得到验证。在这里，我们直接测试是否基底前脑胆碱能神经元是中央的AD调节睡眠驱动管理192-IgG-皂草素损伤BF胆碱能神经元，然后测量AD水平的BF。在BF胆碱能神经元损伤95%的大鼠中，BF中的AD水平不随6 h的延长清醒而增加。然而，损伤大鼠在长时间清醒后6和12 h仍有完整的睡眠驱动，表明BF中的AD积累不是睡眠驱动所必需的。接下来，我们确定，在BF胆碱能神经元缺失的情况下，给予BF的选择性腺苷A（1）受体激动剂N6-环己基腺苷在诱导睡眠方面仍然有效，这表明BF胆碱能神经元对睡眠诱导不是必需的。因此，清醒时BF胆碱能神经元的活动和BF中AD的积累都不是睡眠驱动所必需的。
It is currently hypothesized that the drive to sleep is determined by the activity of the basal forebrain ( BF) cholinergic neurons, which release adenosine ( AD), perhaps because of increased metabolic activity associated with the neuronal discharge during waking, and the accumulating AD begins to inhibit these neurons so that sleep-active neurons can become active. This hypothesis grew from the observation that AD induces sleep and AD levels increase with wake in the basal forebrain, but surprisingly it still remains untested. Here we directly test whether the basal forebrain cholinergic neurons are central to the AD regulation of sleep drive by administering 192-IgG-saporin to lesion the BF cholinergic neurons and then measuring AD levels in the BF. In rats with 95% lesion of the BF cholinergic neurons, AD levels in the BF did not increase with 6 h of prolonged waking. However, the lesioned rats had intact sleep drive after 6 and 12 h of prolonged waking, indicating that the AD accumulation in the BF is not necessary for sleep drive. Next we determined that, in the absence of the BF cholinergic neurons, the selective adenosine A(1) receptor agonist N6-cyclohexyladenosine, administered to the BF, continued to be effective in inducing sleep, indicating that the BF cholinergic neurons are not essential to sleep induction. Thus, neither the activity of the BF cholinergic neurons nor the accumulation of AD in the BF during wake is necessary for sleep drive.