Sceniak Michael P, Maciver M Bruce
Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA.
BMC Neurosci. 2008 Jan 16;9:8. doi: 10.1186/1471-2202-9-8.
Previous reports of inhibition in the neocortex suggest that inhibition is mediated predominantly through GABA(A) receptors exhibiting fast kinetics. Within the hippocampus, it has been shown that GABA(A) responses can take the form of either fast or slow response kinetics. Our findings indicate, for the first time, that the neocortex displays synaptic responses with slow GABA(A) receptor mediated inhibitory postsynaptic currents (IPSCs). These IPSCs are kinetically and pharmacologically similar to responses found in the hippocampus, although the anatomical specificity of evoked responses is unique from hippocampus. Spontaneous slow GABA(A) IPSCs were recorded from both pyramidal and inhibitory neurons in rat visual cortex.
GABA(A) slow IPSCs were significantly different from fast responses with respect to rise times and decay time constants, but not amplitudes. Spontaneously occurring GABA(A) slow IPSCs were nearly 100 times less frequent than fast sIPSCs and both were completely abolished by the chloride channel blocker, picrotoxin. The GABA(A) subunit-specific antagonist, furosemide, depressed spontaneous and evoked GABA(A) fast IPSCs, but not slow GABA(A)-mediated IPSCs. Anatomical specificity was evident using minimal stimulation: IPSCs with slow kinetics were evoked predominantly through stimulation of layer 1/2 apical dendritic zones of layer 4 pyramidal neurons and across their basal dendrites, while GABA(A) fast IPSCs were evoked through stimulation throughout the dendritic arborization. Many evoked IPSCs were also composed of a combination of fast and slow IPSC components.
GABA(A) slow IPSCs displayed durations that were approximately 4 fold longer than typical GABA(A)fast IPSCs, but shorter than GABA(B)-mediated inhibition. The anatomical and pharmacological specificity of evoked slow IPSCs suggests a unique origin of synaptic input. Incorporating GABA(A) slow IPSCs into computational models of cortical function will help improve our understanding of cortical information processing.
先前关于新皮层抑制作用的报告表明，抑制作用主要通过具有快速动力学的GABA(A)受体介导。在海马体中，已表明GABA(A)反应可以采取快速或缓慢反应动力学的形式。我们的研究结果首次表明，新皮层表现出由GABA(A)受体介导的具有缓慢抑制性突触后电流（IPSCs）的突触反应。这些IPSCs在动力学和药理学上与在海马体中发现的反应相似，尽管诱发反应的解剖学特异性与海马体不同。在大鼠视觉皮层的锥体神经元和抑制性神经元中均记录到了自发性缓慢GABA(A) IPSCs。
GABA(A)缓慢IPSCs在上升时间和衰减时间常数方面与快速反应有显著差异，但幅度无差异。自发性GABA(A)缓慢IPSCs的频率比快速sIPSCs低近100倍，并且两者都被氯离子通道阻滞剂印防己毒素完全消除。GABA(A)亚基特异性拮抗剂速尿抑制自发性和诱发的GABA(A)快速IPSCs，但不抑制缓慢的GABA(A)介导的IPSCs。使用最小刺激时解剖学特异性很明显：具有缓慢动力学的IPSCs主要通过刺激第4层锥体神经元的第1/2层顶端树突区域及其基底树突诱发，而GABA(A)快速IPSCs通过整个树突分支的刺激诱发。许多诱发的IPSCs也由快速和缓慢IPSC成分组合而成。
GABA(A)缓慢IPSCs的持续时间比典型的GABA(A)快速IPSCs长约4倍，但比GABA(B)介导的抑制作用短。诱发的缓慢IPSCs的解剖学和药理学特异性表明突触输入的起源独特。将GABA(A)缓慢IPSCs纳入皮质功能的计算模型将有助于提高我们对皮质信息处理的理解。
