The a2A-adrenoceptor suppresses excitatory synaptic transmission to both excitatory and inhibitory neurons in layer 4 barrel cortex
The a2A-adrenoceptor suppresses excitatory synaptic transmission to both excitatory and inhibitory neurons in layer 4 barrel cortex
复制标题
a2A 肾上腺素受体抑制第 4 层桶状皮层中兴奋性和抑制性神经元的兴奋性突触传递
DOI：
10.1113/jp275142
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Fumitaka Kimura
中科院分区：
文献类型：
--
作者：
Minoru Ohshima;Chiaki Itami;Fumitaka Kimura
关键点去甲肾上腺素对兴奋性突触传递到皮层第4层的规则尖峰（兴奋性）细胞以及规则尖峰非锥体细胞和快速尖峰（均为抑制性）细胞的影响在丘脑皮层切片制备中进行了研究，重点是来自丘脑和小鼠桶状皮层第2/3层的垂直输入。然而，离子导入谷氨酸诱导的电流并未受到抑制。此外，成对脉冲比和变异系数分析表明，作用部位是突触前。药理学研究表明，抑制作用是由α2-肾上腺素受体介导的。与此一致，α 2A-肾上腺素能受体基因敲除小鼠证实了α2A-肾上腺素能受体激活参与兴奋性和抑制性细胞的突触抑制。蓝斑的纤维为了确定NA对丘脑腹侧基底层和第2/3层（L2/3）的第4层（L4）细胞的垂直突触输入的影响，制备丘脑皮质切片，并从L4细胞进行全细胞记录。电刺激丘脑或L2/3上方诱发兴奋性突触反应。通过响应电流注射的放电模式，将记录的细胞识别为规则尖峰、规则尖峰非锥体细胞或快速尖峰细胞。NA以剂量依赖性方式抑制（对照的约50%）对所有细胞类型的兴奋性垂直输入。三项独立的研究提出了NA的突触前作用位点。首先，离子电渗应用谷氨酸引起的反应不抑制NA。第二，在NA抑制期间，成对脉冲比率增加。最后，进行了变异系数（CV）分析，CV-2的比值与突触后反应幅度比值的对角线对齐表明了抑制的突触前机制。苯肾上腺素（α1-激动剂）、哌唑嗪（α1-拮抗剂）、育亨宾（α2-拮抗剂）和普萘洛尔（β-拮抗剂）的实验表明，抑制作用由α2-肾上腺素受体介导。为了确定是否涉及α2A-肾上腺素受体亚型，使用α2A-肾上腺素受体敲除小鼠。NA未能抑制所有细胞类型中的EPSC，表明α2A-肾上腺素受体参与。总之，我们得出结论，NA通过突触前α2A-肾上腺素受体抑制L4兴奋性和抑制性细胞中的垂直兴奋性突触连接。
Key pointsThe effects of noradrenaline on excitatory synaptic transmission to regular spiking (excitatory) cells as well as regular spiking non‐pyramidal and fast spiking (both inhibitory) cells in cortical layer 4 were studied in thalamocortical slice preparations, focusing on vertical input from thalamus and layer 2/3 in the mouse barrel cortex.Excitatory synaptic responses were suppressed by noradrenaline. However, currents induced by iontophoretically applied glutamate were not suppressed. Further, paired pulse ratio and coefficient of variation analysis indicated the site of action was presynaptic.Pharmacological studies indicated that the suppression was mediated by the α2‐adrenoceptor.Consistent with this, involvement of α2A‐adrenoceptor activation in the synaptic suppression in excitatory and inhibitory cells was confirmed by the use of α2A‐adrenoceptor knockout mice.AbstractThe mammalian neocortex is widely innervated by noradrenergic (NA) fibres from the locus coeruleus. To determine the effects of NA on vertical synaptic inputs to layer 4 (L4) cells from the ventrobasal thalamus and layer 2/3 (L2/3), thalamocortical slices were prepared and whole‐cell recordings were made from L4 cells. Excitatory synaptic responses were evoked by electrical stimulation of the thalamus or L2/3 immediately above. Recorded cells were identified as regular spiking, regular spiking non‐pyramidal or fast spiking cells through their firing patterns in response to current injections. NA suppressed (∼50% of control) excitatory vertical inputs to all cell types in a dose‐dependent manner. The presynaptic site of action of NA was suggested by three independent studies. First, responses caused by iontophoretically applied glutamate were not suppressed by NA. Second, the paired pulse ratio was increased during NA suppression. Finally, a coefficient of variation (CV) analysis was performed and the resultant diagonal alignment of the ratio of CV−2plotted against the ratio of the amplitude of postsynaptic responses suggests a presynaptic mechanism for the suppression. Experiments with phenylephrine (an α1‐agonist), prazosin (an α1‐antagonist), yohimbine (an α2‐antagonist) and propranolol (a β‐antagonist) indicated that suppression was mediated by the α2‐adrenoceptor. To determine whether the α2A‐adrenoceptor subtype was involved, α2A‐adrenoceptor knockout mice were used. NA failed to suppress EPSCs in all cell types, suggesting an involvement of the α2A‐adrenoceptor. Altogether, we concluded that NA suppresses vertical excitatory synaptic connections in L4 excitatory and inhibitory cells through the presynaptic α2A‐adrenoceptor.