GABAB receptor activation modulates GABAA receptor-mediated lnhibition in chicken nucleus magnocellularis neurons
GABAB receptor activation modulates GABAA receptor-mediated lnhibition in chicken nucleus magnocellularis neurons
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DOI：
10.1152/jn.00786.2004
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发表时间：
2005-03-01
影响因子：
2.5
通讯作者：
Rubel, EW
中科院分区：
文献类型：
--
作者：
Lu, Y;Burger, RM;Rubel, EW
大细胞核(NM)是鸟类耳蜗核的一个分支，执行精确的时间编码，其神经元只接受来自第八神经的谷氨酸能兴奋性输入和主要来自同侧上橄榄核的GABA能抑制性输入。GABA既能激活配体门控的氯离子通道[GABA(A)受体(GABA(A)Rs)]，又能激活G A蛋白偶联受体(GABA(B)受体)。GABA(A)受体对NM的净效应是抑制的，虽然是去极化的。一些研究表明，这种分流的、抑制性的GABA能输入可以在突触后NM神经元中诱发动作电位，这可能会干扰它们的时间编码。而这种GABA介导的放电受到低电压激活的K+电导的限制。我们已经找到了第二种机制的证据。我们使用全细胞记录技术研究了GABA(B)受体对GABA，R介导的反应的调制。巴氯芬是一种GABA(B)受体激动剂，对诱发的抑制性突触后电流(EIPSCs)具有剂量依赖性抑制作用。这种抑制作用可被GABA(B)R拮抗剂CGP52432阻断。巴氯芬降低微型IPSCs(MIPSCs)的频率，但不降低mIPSCs的幅度，也不影响喷雾应用GABA(A)R激动剂Muscimol引起的突触后电流，提示GABA(B)R介导的调制是突触前机制。刺激突触GABA对NM神经元的放电作用可被巴氯芬消除。但在突触前抑制终末未观察到内源性GABA(B)R活性。我们认为，突触前GABA(B)受体起自身受体的作用，调节GABA(A)R抑制的突触强度，并阻止NM神经元在激活抑制传入时产生放电。
Neurons of nucleus magnocellularis (NM), a division of avian cochlear nucleus that performs precise temporal encoding, receive glutamatergic excitatory input solely from the eighth nerve and GABAergic inhibitory input primarily from the ipsilateral superior olivary nucleus. GABA activates both ligand-gated Cl- channels [GABA(A) receptors (GABA(A)Rs)] and G A Aprotein-coupled receptors (GABA(B) receptors). The net effect of GABA(A)R-inediated input to NM is inhibitory, although depolarizing. Several Studies have shown that this shunting, inhibitory GABAergic input can evoke action potentials in postsynaptic NM neurons, which could interfere with their temporal encoding. While this GABA-mediated firing is limited by a low-voltage-activated K+ conductance. we have found evidence for a second mechanism. We investigated modulation of GABA,R-mediated responses by GABA(B)Rs using whole cell recording techniques. Bath-applied baclofen, a GABA(B)R agonist, produced dose-dependent suppression of evoked inhibitory postsynaptic currents (eIPSCs). This suppression was blocked by CGP52432, a potent and selective GABA(B)R antagonist. Baclofen reduced the frequency but not the amplitude of miniature IPSCs (mIPSCs) and did not affect postsynaptic currents elicited by puff application of a specific GABA(A)R agonist muscimol, suggesting a presynaptic mechanism for the GABA(B)R-mediated modulation. Firing of NM neurons by synaptic stimulation of GABAergic inputs to NM was eliminated by baclofen. However, endogenous GABA(B)R activity in the presynaptic inhibitory terminals was not observed. We propose that presynaptic GABA(B)Rs function as autoreceptors, regulating synaptic strength of GABA(A)R-rnediated inhibition, and prevent NM neurons from generating firing during activation of the inhibitory inputs.