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脊髓 I 层中两种表达神经激肽 1 受体的投射神经元,其 AMPA 受体亚基组成和兴奋性突触传入密度不同。

Two populations of neurokinin 1 receptor-expressing projection neurons in lamina I of the rat spinal cord that differ in AMPA receptor subunit composition and density of excitatory synaptic input.

机构信息

Neuroscience and Molecular Pharmacology, Faculty of Biomedical and Life Sciences, West Medical Building, University Avenue, University of Glasgow, Glasgow G12 8QQ, UK.

出版信息

Neuroscience. 2010 Jun 2;167(4):1192-204. doi: 10.1016/j.neuroscience.2010.03.028. Epub 2010 Mar 18.

Abstract

Lamina I of the spinal cord contains many projection neurons that express the neurokinin 1 receptor (NK1r). It has been reported that these cells can undergo long-term potentiation (LTP), which may result from insertion of AMPA-type glutamate receptors (AMPArs) containing GluA1 or GluA4 subunits. We therefore investigated synaptic AMPAr expression on these cells with immunocytochemistry following antigen-retrieval. We also examined their density of glutamatergic input (by analysing AMPAr synaptic puncta and contacts from glutamatergic boutons), and phosphorylation of extracellular signal-regulated kinases (pERKs) following noxious stimulation. Our results indicate that there are two populations of NK1r-expressing projection neurons: large GluA4(+)/GluA1(-) cells with a high density of glutamatergic input and small GluA1(+)/GluA4(-) cells with a much lower input density. Results from pERK experiments suggested that the two groups may not differ in the types of noxious stimulus that activate them. Glutamatergic synapses on distal dendrites of the large cells were significantly longer than those on proximal dendrites, which presumably compensates for the greater attenuation of distally-generated excitatory postsynaptic currents (EPSCs). Both types of cell received contacts from peptidergic primary afferents, however, on the large cells these appeared to constitute over half of the glutamatergic synapses, and were often associated with elongated AMPAr puncta. This suggests that these afferents, which probably contain substance P, provide a powerful, secure synaptic input to large NK1r-expressing projection neurons. These results demonstrate the importance of GluA4-containing AMPArs in nociceptive transmission and raise the possibility that different forms of LTP in lamina I projection neurons may be related to differential expression of GluA1/GluA4.

摘要

脊髓 I 层包含许多表达神经激肽 1 受体 (NK1r) 的投射神经元。据报道,这些细胞可以经历长时程增强 (LTP),这可能是由于 AMPA 型谷氨酸受体 (AMPAr) 的插入,这些受体包含 GluA1 或 GluA4 亚基。因此,我们通过抗原回收后的免疫细胞化学研究了这些细胞上的突触 AMPAr 表达。我们还检查了它们的谷氨酸能输入密度(通过分析 AMPAr 突触小泡和谷氨酸能末梢的接触),以及伤害性刺激后的细胞外信号调节激酶 (pERK) 的磷酸化。我们的结果表明,NK1r 表达的投射神经元有两种群体:谷氨酸能输入密度高的大 GluA4(+)/GluA1(-) 细胞和输入密度低得多的小 GluA1(+)/GluA4(-) 细胞。pERK 实验的结果表明,这两组细胞在激活它们的伤害性刺激类型上可能没有差异。大细胞远端树突上的谷氨酸能突触明显长于近端树突上的突触,这可能补偿了远端产生的兴奋性突触后电流 (EPSC) 的更大衰减。这两种类型的细胞都接收来自肽能初级传入的接触,但在大细胞上,这些接触似乎构成了谷氨酸能突触的一半以上,并且经常与伸长的 AMPAr 小泡相关。这表明这些可能包含 P 物质的传入神经,为大 NK1r 表达投射神经元提供了强大、安全的突触输入。这些结果表明,含有 GluA4 的 AMPAr 在伤害性传递中的重要性,并提出了 I 层投射神经元中不同形式的 LTP 可能与 GluA1/GluA4 的差异表达有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d8/3169794/9632157c5555/gr1.jpg

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