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激活突触前 GABAB 受体调节内侧膝状体的 GABA 能和谷氨酸能传入。

Activation of presynaptic GABAB receptors modulates GABAergic and glutamatergic inputs to the medial geniculate body.

机构信息

CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.

出版信息

Hear Res. 2011 Oct;280(1-2):157-65. doi: 10.1016/j.heares.2011.05.018. Epub 2011 May 31.

Abstract

The medial geniculate body (MGB) receives ascending inputs from the inferior colliculus and descending inputs from the auditory cortex. In the present study, we intended to determine whether activation of presynaptic GABA(B) receptors modulates GABAergic and glutamatergic inputs to the MGB with whole-cell patch-clamp recordings in brain slices of the rat. To evoke a synaptic response, we electrically stimulated the ascending and descending inputs to MGB neurons with bipolar electrodes placed on the brachium of the inferior colliculus and the superior thalamic radiation. To isolate presynaptic mechanisms, we blocked the effects of postsynaptic GABA(B) receptors by filling recording electrodes with the internal solution containing cesium and QX-314. The activation of presynaptic GABA(B) receptors by exogenous agonist was shown to modulate synaptic inputs to the MGB as demonstrated by that (1) baclofen, a GABA(B) receptor agonist, reversibly suppressed both inhibitory postsynaptic currents (IPSCs) and excitatory postsynaptic currents (EPSCs) and this suppressive effect could be blocked by CGP35348, a GABA(B) receptor antagonist, (2) baclofen significantly increased the ratio of IPSCs or EPSCs elicited by paired-pulse stimulation, and (3) baclofen depressed EPSCs and IPSCs in response to repetitive stimulation. The activation of presynaptic GABA(B) receptors by endogenously released GABA was shown to modulate the synaptic transmission as demonstrated by that CGP55845, another GABA(B) receptor antagonist, increased the ratio of IPSCs to paired-pulse stimulation in young (P8-10) rats, although not in juvenile (P15-18) rats. Our study provides electrophysiological evidence for the presence of functional presynaptic GABA(B) receptors in the MGB and suggests an age-dependent role of these receptors in the synaptic transmission in this central auditory region.

摘要

内侧膝状体(MGB)接收来自下丘的传入输入和来自听觉皮层的传出输入。在本研究中,我们旨在通过在大鼠脑切片上进行全细胞膜片钳记录来确定激活突触前 GABA(B) 受体是否调节 MGB 的 GABA 能和谷氨酸能传入。为了引发突触反应,我们用电极刺激 MGB 神经元的传入输入,这些电极放置在下丘臂和上丘脑辐射上。为了分离突触前机制,我们通过在记录电极中填充含有铯和 QX-314 的内部溶液来阻断突触后 GABA(B) 受体的作用。外源性激动剂激活突触前 GABA(B) 受体可调节 MGB 的突触输入,这表现在以下方面:(1)GABA(B) 受体激动剂巴氯芬可可逆地抑制抑制性突触后电流(IPSCs)和兴奋性突触后电流(EPSCs),这种抑制作用可被 GABA(B) 受体拮抗剂 CGP35348 阻断,(2)巴氯芬显著增加了由成对刺激引起的 IPSCs 或 EPSCs 的比率,(3)巴氯芬在重复刺激时抑制 EPSCs 和 IPSCs。内源性释放的 GABA 激活突触前 GABA(B) 受体可调节突触传递,这表现在另一种 GABA(B) 受体拮抗剂 CGP55845 增加了年轻(P8-10 天)大鼠中 IPSCs 与成对刺激的比率,尽管在幼年(P15-18 天)大鼠中没有增加。我们的研究为 MGB 中存在功能性突触前 GABA(B) 受体提供了电生理学证据,并表明这些受体在该中枢听觉区域的突触传递中具有年龄依赖性作用。

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