Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
J Physiol. 2014 Feb 15;592(4):759-76. doi: 10.1113/jphysiol.2013.264937. Epub 2013 Dec 9.
Interneurons of the spinal dorsal horn are central to somatosensory and nociceptive processing. A mechanistic understanding of their function depends on profound knowledge of their intrinsic properties and their integration into dorsal horn circuits. Here, we have used BAC transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the vesicular glutamate transporter (vGluT2) gene (vGluT2::eGFP mice) to perform a detailed electrophysiological and morphological characterisation of excitatory dorsal horn neurons, and to compare their properties to those of GABAergic (Gad67::eGFP tagged) and glycinergic (GlyT2::eGFP tagged) neurons. vGluT2::eGFP was detected in about one-third of all excitatory dorsal horn neurons and, as demonstrated by the co-expression of vGluT2::eGFP with different markers of subtypes of glutamatergic neurons, probably labelled a representative fraction of these neurons. Three types of dendritic tree morphologies (vertical, central, and radial), but no islet cell-type morphology, were identified in vGluT2::eGFP neurons. vGluT2::eGFP neurons had more depolarised action potential thresholds and longer action potential durations than inhibitory neurons, while no significant differences were found for the resting membrane potential, input resistance, cell capacitance and after-hyperpolarisation. Delayed firing and single action potential firing were the single most prevalent firing patterns in vGluT2::eGFP neurons of the superficial and deep dorsal horn, respectively. By contrast, tonic firing prevailed in inhibitory interneurons of the dorsal horn. Capsaicin-induced synaptic inputs were detected in about half of the excitatory and inhibitory neurons, and occurred more frequently in superficial than in deep dorsal horn neurons. Primary afferent-evoked (polysynaptic) inhibitory inputs were found in the majority of glutamatergic and glycinergic neurons, but only in less than half of the GABAergic population. Excitatory dorsal horn neurons thus differ from their inhibitory counterparts in several biophysical properties and possibly also in their integration into the local neuronal circuitry.
脊髓背角的中间神经元是躯体感觉和伤害性感受处理的核心。对其功能的机制理解取决于对其内在特性及其整合到背角回路中的深刻认识。在这里,我们使用表达增强型绿色荧光蛋白(eGFP)的 BAC 转基因小鼠,该蛋白受囊泡谷氨酸转运体(vGluT2)基因的控制(vGluT2::eGFP 小鼠),对兴奋性背角神经元进行详细的电生理和形态特征分析,并将其特性与 GABA 能(Gad67::eGFP 标记)和甘氨酸能(GlyT2::eGFP 标记)神经元进行比较。vGluT2::eGFP 在大约三分之一的兴奋性背角神经元中被检测到,并且正如 vGluT2::eGFP 与不同的谷氨酸能神经元亚型标志物的共表达所证明的那样,它可能代表了这些神经元的一部分。在 vGluT2::eGFP 神经元中鉴定出三种树突形态(垂直、中央和放射状),但没有胰岛细胞类型的形态。vGluT2::eGFP 神经元的动作电位阈值更去极化,动作电位持续时间更长,而抑制性神经元的静息膜电位、输入电阻、细胞电容和后超极化没有明显差异。延迟放电和单动作电位放电分别是浅层和深层背角 vGluT2::eGFP 神经元最常见的放电模式。相比之下,强直放电在背角抑制性中间神经元中占主导地位。约一半的兴奋性和抑制性神经元检测到辣椒素诱导的突触输入,且在浅层背角神经元中比在深层背角神经元中更频繁。在大多数谷氨酸能和甘氨酸能神经元中发现了初级传入诱发的(多突触)抑制性输入,但在 GABA 能神经元中只有不到一半的神经元中发现了这种输入。兴奋性背角神经元在几个生物物理特性上与它们的抑制性神经元不同,并且可能也在它们整合到局部神经元回路中有所不同。