Price Christopher J, Scott Ricardo, Rusakov Dmitri A, Capogna Marco
Medical Research Council Anatomical Neuropharmacology Unit, Oxford OX1 3TH, United Kingdom.
J Neurosci. 2008 Jul 2;28(27):6974-82. doi: 10.1523/JNEUROSCI.4673-07.2008.
Feedforward inhibition of neurons is a fundamental component of information flow control in the brain. We studied the roles played by neurogliaform cells (NGFCs) of stratum lacunosum moleculare of the hippocampus in providing feedforward inhibition to CA1 pyramidal cells. We recorded from synaptically coupled pairs of anatomically identified NGFCs and CA1 pyramidal cells and found that, strikingly, a single presynaptic action potential evoked a biphasic unitary IPSC (uIPSC), consisting of two distinct components mediated by GABA(A) and GABA(B) receptors. A GABA(B) receptor-mediated unitary response has not previously been observed in hippocampal excitatory neurons. The decay of the GABA(A) receptor-mediated response was slow (time constant = 50 ms), and was tightly regulated by presynaptic GABA(B) receptors. Surprisingly, the GABA(B) receptor ligands baclofen and (2S)-3-{[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl}(phenylmethyl)phosphinic acid (CGP55845), while affecting the NGFC-mediated uIPSCs, had no effect on action potential-evoked presynaptic Ca2+ signals monitored in individual axonal boutons of NGFCs with two-photon microscopy. In contrast, baclofen clearly depressed presynaptic Ca2+ transients in non-NGF interneurons. Changes in extracellular Ca2+ concentration that mimicked the effects of baclofen or CGP55845 on uIPSCs significantly altered presynaptic Ca2+ transients. Electrophysiological data suggest that GABA(B) receptors expressed by NGFCs contribute to the dynamic control of the excitatory input to CA1 pyramidal neurons from the temporoammonic path. The NGFC-CA1 pyramidal cell connection therefore provides a unique and subtle mechanism to shape the integration time domain for signals arriving via a major excitatory input to CA1 pyramidal cells.
神经元的前馈抑制是大脑信息流控制的一个基本组成部分。我们研究了海马分子层隙状层的神经胶质样细胞（NGFCs）在对CA1锥体细胞提供前馈抑制中所起的作用。我们记录了在解剖学上已鉴定的NGFCs和CA1锥体细胞的突触耦合对，并且惊人地发现，单个突触前动作电位诱发了一个双相的单位抑制性突触后电流（uIPSC），它由由GABA(A)和GABA(B)受体介导的两个不同成分组成。此前在海马兴奋性神经元中尚未观察到GABA(B)受体介导的单位反应。GABA(A)受体介导的反应的衰减很慢（时间常数 = 50毫秒），并且受到突触前GABA(B)受体的严格调节。令人惊讶的是，GABA(B)受体配体巴氯芬和(2S)-3-{[(1S)-1-(3,4-二氯苯基)乙基]氨基-2-羟丙基}(苯甲基)次膦酸（CGP55845），虽然影响NGFC介导的uIPSCs，但对用双光子显微镜在NGFCs的单个轴突终扣中监测到的动作电位诱发的突触前Ca2+信号没有影响。相比之下，巴氯芬明显抑制非NGF中间神经元中的突触前Ca2+瞬变。模拟巴氯芬或CGP55845对uIPSCs作用的细胞外Ca2+浓度变化显著改变了突触前Ca2+瞬变。电生理数据表明，NGFCs表达的GABA(B)受体有助于动态控制来自颞叶-海马通路的对CA1锥体细胞的兴奋性输入。因此，NGFC-CA1锥体细胞连接提供了一种独特而微妙的机制，以塑造通过对CA1锥体细胞的主要兴奋性输入到达的信号的整合时域。
