Adenosine-mediated presynaptic modulation of glutamatergic transmission in the laterodorsal tegmentum
Adenosine-mediated presynaptic modulation of glutamatergic transmission in the laterodorsal tegmentum
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DOI：
10.1523/jneurosci.21-03-01076.2001
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发表时间：
2001-02-01
影响因子：
5.3
通讯作者：
Greene, RW
中科院分区：
文献类型：
--
作者：
Arrigoni, E;Rainnie, DG;Greene, RW
外侧背被盖(LDT)神经元为脑干和间脑提供生理唤醒所需的大部分胆碱能张力。众所周知，在体内将腺苷应用于LDT核可增加睡眠(Portas等人，1997)，并在体外通过激活突触后腺苷A(1)受体直接抑制LDT神经元(Rainnie等人，1994)。然而，腺苷对LDT神经元突触输入的影响尚未见报道。我们发现，腺苷(50微米)对诱发的谷氨酸能EPSCs和GABA能IPSCs均有抑制作用。腺苷A(1)受体在谷氨酸能传入的突触前作用部位如下：(1)腺苷不影响外源性谷氨酸介导的电流；(2)腺苷降低谷氨酸能小型突触后干细胞(MEPSC)的频率，但不影响其幅度；(3)A(1)激动剂N6-环己基腺苷(100 NM)可模拟抑制诱发的小型EPSC，但A(2)激动剂N6-[2-(3，5-dimethoxyphenyl)-2-(methylphenyl)-ethyl]-adenosine(10 NM)不能。200 nM)可增强诱发的EPSCs，提示内源性腺苷对突触前A(1)受体有紧张性激活作用。腺苷激酶抑制剂，5-碘结节杀菌素(10微米)，模拟腺苷突触前和突触后效应。这些作用可被CPT或腺苷脱氨酶(0.8IU/ml)所拮抗，提示可通过增加细胞外内源性腺苷进行调节。综上所述，这些结果表明，LDT神经元的活动受到内源性腺苷的抑制，内源性腺苷通过激活兴奋性终末上的突触前A(1)受体和突触后A(1)受体来抑制LDT神经元的活动。此外，腺苷激酶活性的改变改变了这种抑制音的程度。
The laterodorsal tegmentum (LDT) neurons supply most of the cholinergic tone to the brainstem and diencephalon necessary for physiological arousal. It is known that application of adenosine in the LDT nucleus increases sleep in vivo (Portas et al., 1997) and directly inhibits LDT neurons in vitro by activating postsynaptic adenosine A(1) receptors (Rainnie et al., 1994). However, adenosine effects on synaptic inputs to LDT neurons has not been previously reported. We found that both evoked glutamatergic EPSCs and GABAergic IPSCs were reduced by adenosine (50 muM). A presynaptic site of action for adenosine A(1) receptors on glutamatergic afferents was suggested by the following: (1) adenosine did not affect exogenous glutamate-mediated current, (2) adenosine reduced glutamatergic miniature EPSC (mEPSC) frequency, without affecting the amplitude, and (3) inhibition of the evoked EPSC was mimicked by the A(1) agonist N6-cyclohexyladenosine (100 nM) but not by the A(2) agonist N6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)-ethyl]-adenosine (10 nM).The A(1) receptor antagonist 8-cyclopentyltheophylline (CPT; 200 nM) potentiated the evoked EPSCs, suggesting the presence of a tonic activation of presynaptic A(1) receptors by endogenous adenosine. The adenosine kinase inhibitor, 5-iodotubercidin (10 muM), mimicked adenosine presynaptic and postsynaptic effects. These effects were antagonized by CPT or adenosine deaminase (0.8 IU/ ml), suggesting mediation by increased extracellular endogenous adenosine. Together, these data suggest that the activity of LDT neurons is under inhibitory tone by endogenous adenosine through the activation of both presynaptic A(1) receptors on excitatory terminals and postsynaptic A(1) receptors. Furthermore, an alteration of adenosine kinase activity modifies the degree of this inhibitory tone.