Department of Psychology, University of Connecticut, Storrs, CT 06269, USA.
Neuroscience. 2014 Feb 28;260:171-84. doi: 10.1016/j.neuroscience.2013.12.018. Epub 2013 Dec 16.
Adenosine is a wide-spread endogenous neuromodulator. In the central nervous system it activates A1 and A2A receptors (A1Rs and A2ARs) which have differential distributions, different affinities to adenosine, are coupled to different G-proteins, and have opposite effects on synaptic transmission. Although effects of adenosine are studied in detail in several brain areas, such as the hippocampus and striatum, the heterogeneity of the effects of A1R and A2AR activation and their differential distribution preclude generalization over brain areas and cell types. Here we study adenosine's effects on excitatory synaptic transmission to layer 2/3 pyramidal neurons in slices of the rat visual cortex. We measured effects of bath application of adenosine receptor ligands on evoked excitatory postsynaptic potentials (EPSPs), miniature excitatory postsynaptic potentials (mEPSPs), and membrane properties. Adenosine reduced the amplitude of evoked EPSPs and excitatory postsynaptic currents (EPSCs), and reduced frequency of mEPSPs in a concentration-dependent and reversible manner. Concurrent with EPSP/C amplitude reduction was an increase in the paired-pulse ratio. These effects were blocked by application of the selective A1R antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine), suggesting that activation of presynaptic A1Rs suppresses excitatory transmission by reducing release probability. Adenosine (20μM) hyperpolarized the cell membrane from -65.3±1.5 to -67.7±1.8mV, and reduced input resistance from 396.5±44.4 to 314.0±36.3MOhm (∼20%). These effects were also abolished by DPCPX, suggesting postsynaptic A1Rs. Application of the selective A2AR antagonist SCH-58261 (2-(2-furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-a-mine) on the background of high adenosine concentrations revealed an additional decrease in EPSP amplitude. Moreover, application of the A2AR agonist CGS-21680 (4-[2-[[6-amino-9-(N-ethyl-β-d-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid hydrochloride) led to an A1R-dependent increase in mEPSP frequency. Dependence of the A2AR effects on the A1R availability suggests interaction between these receptors, whereby A2ARs exert their facilitatory effect on synaptic transmission by inhibiting the A1R-mediated suppression. Our results demonstrate functional pre and postsynaptic A1Rs and presynaptic A2ARs in layer 2/3 of the visual cortex, and suggest interaction between presynaptic A2ARs and A1Rs.
腺苷是一种广泛存在的内源性神经调质。在中枢神经系统中，它激活 A1 和 A2A 受体（A1R 和 A2AR），这些受体具有不同的分布、对腺苷的不同亲和力、与不同的 G 蛋白偶联，并且对突触传递有相反的影响。尽管腺苷的作用在海马体和纹状体等几个脑区进行了详细研究，但 A1R 和 A2AR 激活的作用的异质性及其差异分布排除了对脑区和细胞类型的概括。在这里，我们研究了腺苷对大鼠视觉皮层切片中 2/3 层锥体神经元兴奋性突触传递的影响。我们测量了在浴中应用腺苷受体配体对诱发的兴奋性突触后电位（EPSP）、微小兴奋性突触后电位（mEPSP）和膜特性的影响。腺苷以浓度依赖和可逆的方式降低诱发的 EPSP 和兴奋性突触后电流（EPSC）的幅度，并降低 mEPSP 的频率。与 EPSP/C 幅度降低同时发生的是成对脉冲比的增加。这些作用被选择性 A1R 拮抗剂 DPCPX（8-环戊基-1,3-二丙基黄嘌呤）的应用所阻断，表明激活突触前 A1R 通过降低释放概率来抑制兴奋性传递。腺苷（20μM）将细胞膜从-65.3±1.5 超极化至-67.7±1.8mV，并将输入电阻从 396.5±44.4 降低至 314.0±36.3MOhm（约 20%）。这些作用也被 DPCPX 消除，表明突触后 A1R。在高腺苷浓度背景下应用选择性 A2AR 拮抗剂 SCH-58261（2-（2-呋喃基）-7-（2-苯乙基）-7H-吡唑并[4,3-e][1,2,4]三唑[1,5-c]嘧啶-5-a-甲胺）导致 EPSP 幅度进一步降低。此外，应用 A2AR 激动剂 CGS-21680（4-[[6-氨基-9-（N-乙基-β-D-呋喃核糖基）氨基]-9H-嘌呤-2-基]氨基]乙基）苯丙酸盐酸盐）导致 mEPSP 频率的 A1R 依赖性增加。A2AR 作用对 A1R 可用性的依赖性表明这些受体之间存在相互作用，其中 A2AR 通过抑制 A1R 介导的抑制来发挥对突触传递的促进作用。我们的结果表明在视觉皮层 2/3 层中存在功能性的突触前和突触后 A1R 和突触前 A2AR，并表明突触前 A2AR 和 A1R 之间存在相互作用。
