Wolansky Trish, Pagliardini Silvia, Greer John J, Dickson Clayton T
Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada T6G 2R3.
J Comp Neurol. 2007 May 20;502(3):427-41. doi: 10.1002/cne.21338.
It has been reported that application of substance P (SP) to the medial portion of the entorhinal cortex (EC) induces a powerful antiepileptic effect (Maubach et al. [1998] Neuroscience 83:1047-1062). This effect is presumably mediated via inhibitory interneurons expressing the neurokinin-1 receptor (NK(1)R), but the existence of NK(1)R-expressing inhibitory interneurons in the EC has not yet been reported. The present immunohistochemical study was performed in the rat to examine the existence and distribution of NK(1)R-expressing neurons in the EC as well as any co-expression of other neurotransmitters/neuromodulators known to be associated with inhibitory interneurons: gamma-aminobutyric acid (GABA), parvalbumin (PARV), calretinin (CT), calbindin (CB), somatostatin (SST), and neuropeptide Y (NPY). Our results indicated that NK(1)R-positive neurons were distributed rather sparsely (especially in the medial EC), primarily in layers II, V, and VI. The results of our double-immunohistochemical staining indicated that the vast majority of NK(1)R-expressing neurons also expressed GABA, SST, and NPY. In addition, CT was co-expressed in a weakly stained subgroup of NK(1)R-expressing neurons, and CB was co-expressed very rarely in the lateral EC, but not in the medial EC. In contrast, SP-immunopositive axons with fine varicosities were distributed diffusely throughout all layers of the EC, appearing to radiate from the angular bundle. SP may be released in a paracrine manner to activate a group of NK(1)R-expressing entorhinal neurons that co-express GABA, SST, and NPY, exerting a profound inhibitory influence on synchronized network activity in the EC.
据报道,将P物质(SP)应用于内嗅皮质(EC)的内侧部分可诱导强大的抗癫痫作用(Maubach等人,[1998]《神经科学》83:1047 - 1062)。这种作用可能是通过表达神经激肽-1受体(NK(1)R)的抑制性中间神经元介导的,但EC中表达NK(1)R的抑制性中间神经元的存在尚未见报道。本免疫组织化学研究在大鼠中进行,以检查EC中表达NK(1)R的神经元的存在和分布,以及已知与抑制性中间神经元相关的其他神经递质/神经调质的共表达情况:γ-氨基丁酸(GABA)、小白蛋白(PARV)、钙视网膜蛋白(CT)、钙结合蛋白(CB)、生长抑素(SST)和神经肽Y(NPY)。我们的结果表明,NK(1)R阳性神经元分布较为稀疏(尤其是在内侧EC),主要分布在II、V和VI层。我们的双重免疫组织化学染色结果表明,绝大多数表达NK(1)R的神经元也表达GABA、SST和NPY。此外,CT在表达NK(1)R的神经元的一个弱阳性亚组中共表达,而CB在外侧EC中很少共表达,但在内侧EC中不共表达。相比之下,具有细小膨体的SP免疫阳性轴突广泛分布于EC的所有层,似乎从角束发出。SP可能以旁分泌方式释放,以激活一组共表达GABA、SST和NPY的表达NK(1)R的内嗅神经元,对EC中的同步网络活动产生深远的抑制作用。