Fontanez D E, Porter J T
Department of Physiology and Pharmacology, Ponce School of Medicine, PO Box 7004, Ponce, Puerto Rico 00732.
Neuroscience. 2006;137(4):1177-84. doi: 10.1016/j.neuroscience.2005.10.022. Epub 2005 Dec 15.
Caffeine is consumed worldwide to enhance wakefulness, but the cellular mechanisms are poorly understood. Caffeine blocks adenosine receptors suggesting that adenosine decreases cortical arousal. Given the widespread innervation of the cerebral cortex by thalamic fibers, adenosine receptors on thalamocortical terminals could provide an efficient method of limiting thalamic activation of the cortex. Using a mouse thalamocortical slice preparation and whole-cell patch clamp recordings, we examined whether thalamocortical terminals are modulated by adenosine receptors. Bath application of adenosine decreased excitatory postsynaptic currents elicited by stimulation of the ventrobasal thalamus. Thalamocortical synapses onto inhibitory and excitatory neurons were equally affected by adenosine. Adenosine also increased the paired pulse ratio and the coefficient of variation of the excitatory postsynaptic currents, suggesting that adenosine decreased glutamate release. The inhibition produced by adenosine was reversed by a selective antagonist of adenosine A1 receptors (8-cyclopentyltheophylline) and mimicked by a selective A1 receptor agonist (N6-cyclopentyladenosine). Our results indicate that thalamocortical excitation is regulated by presynaptic adenosine A1 receptors and provide a mechanism by which increased adenosine levels can directly reduce cortical excitability.
全世界的人都通过摄入咖啡因来提高清醒度，但其中的细胞机制却鲜为人知。咖啡因会阻断腺苷受体，这表明腺苷会降低皮层觉醒。鉴于丘脑纤维对大脑皮层的广泛支配，丘脑皮质终末上的腺苷受体可能提供了一种限制丘脑对皮层激活的有效方法。我们使用小鼠丘脑皮质脑片标本和全细胞膜片钳记录技术，研究了丘脑皮质终末是否受腺苷受体的调节。在浴槽中施加腺苷可降低腹侧基底丘脑刺激所诱发的兴奋性突触后电流。腺苷对丘脑皮质与抑制性和兴奋性神经元形成的突触产生同等影响。腺苷还增加了配对脉冲比率和兴奋性突触后电流的变异系数，这表明腺苷减少了谷氨酸的释放。腺苷产生的抑制作用可被腺苷A1受体的选择性拮抗剂（8-环戊基茶碱）逆转，并被选择性A1受体激动剂（N6-环戊基腺苷）模拟。我们的结果表明，丘脑皮质兴奋受突触前腺苷A1受体的调节，并提供了一种机制，通过该机制，升高的腺苷水平可直接降低皮层兴奋性。
