GABAB receptor modulation of excitatory and inhibitory synaptic transmission onto rat CA3 hippocampal interneurons
GABAB receptor modulation of excitatory and inhibitory synaptic transmission onto rat CA3 hippocampal interneurons
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DOI：
10.1113/jphysiol.2002.034017
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发表时间：
2003-01-15
影响因子：
5.5
通讯作者：
McBain, CJ
中科院分区：
文献类型：
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作者：
Lei, SB;McBain, CJ
海马辐射层抑制性中间神经元通过CA 3区锥体神经元的返侧支纤维接受海马能兴奋性神经支配，并接受来自其他中间神经元的GABA能抑制。我们研究了两种突触类型的突触前和突触后GABA（B）受体介导的反应。突触后GABA（B）受体介导的反应在年轻（P16-18）的记录中不存在，但在老年动物（大于或等于P30）的记录中存在，表明发育调节。在幼年动物中，GABA（B）受体激动剂巴氯芬抑制诱发的EPSC和IPSC的振幅，这种作用可通过预先应用选择性拮抗剂CGP 55845来阻断。巴氯芬增强诱发EPSC和IPSC的成对脉冲比和变异系数，与突触前调节机制一致。此外，巴氯芬降低了微型IPSC的频率，但不是mEPSC。然而，巴氯芬降低KCl诱导的mEPSC的频率; Cd 2+阻断了这种效应，暗示突触前电压门控Ca 2+通道是巴氯芬调节的靶点。相反，尽管Cd 2+阻止了KCl诱导的mIPSC频率的增加，但它未能阻止巴氯芬降低mIPSC频率。N型和P/Q型Ca 2+通道对GABAB受体介导的EPSC抑制的贡献相当，而P/Q型Ca 2+通道更多地参与GABA（B）受体介导的IPSC抑制。最后，巴氯芬阻断了EPSC和IPSC的频率依赖性抑制，但阻断EPSC的频率依赖性易化效果较差。我们的研究结果表明，突触前GABA（B）受体的兴奋性和抑制性突触到CA 3中间神经元的终端上表达，它们的激活调制的释放过程中的基本组成部分，在这两种突触类型的传输。
Hippocampal stratum radiatum inhibitory interneurons receive glutamatergic excitatory innervation via the recurrent collateral fibers of CA3 pyramidal neurons and GABAergic inhibition from other interneurons. We examined both presynaptic- and postsynaptic-GABA(B) receptor-mediated responses at both synapse types. Postsynaptic GABA(B) receptor-mediated responses were absent in recordings from young (P16-18) but present in recordings from older animals (greater than or equal toP30) suggesting developmental regulation. In young animals, the GABA(B) receptor agonist, baclofen, inhibited the amplitude of evoked EPSCs and IPSCs, an effect blocked by prior application of the selective antagonist CGP55845. Baclofen enhanced the paired-pulse ratio and coefficient of variation of evoked EPSCs and IPSCs, consistent with a presynaptic mechanism of regulation. In addition, baclofen reduced the frequency of miniature IPSCs but not mEPSCs. However, baclofen reduced the frequency of KCl-induced mEPSCs; an effect blocked by Cd2+, implicating presynaptic voltage-gated Ca2+ channels as a target for baclofen modulation. In contrast, although Cd2+ prevented the KCl-induced increase in mIPSC frequency, it failed to block baclofen's reduction of mIPSC frequency. Whereas N- and P/Q-types of Ca2+ channels contributed equally to GABAB receptor-mediated inhibition of EPSCs, more P/Q-type Ca2+ channels were involved in GABA(B) receptor-mediated inhibition of IPSCs. Finally, baclofen blocked the frequency-dependent depression of EPSCs and IPSCs, but was less effective at blocking frequency-dependent facilitation of EPSCs. Our results demonstrate that presynaptic GABA(B) receptors are expressed on the terminals of both excitatory and inhibitory synapses onto CA3 interneurons and that their activation modulates essential components of the release process underlying transmission at these two synapse types.