Wilson D A, Sullivan R M, Gall C M, Guthrie K M
Department of Zoology, University of Oklahoma, Norman 73019, USA.
Brain Res. 1996 May 6;719(1-2):62-71. doi: 10.1016/0006-8993(96)00083-2.
Olfactory bulb primary output neurons, mitral/tufted cells, are glutamatergic and excite inhibitory interneurons, granule cells, by activation of both alpha-amino-3-hydroxy-5-methyl-ioxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors. The data presented here demonstrate that the NMDA antagonists MK-801 and CGP39551, but not ketamine, significantly enhanced expression of c-fos mRNA by mitral cells as measured by in situ hybridization. All three antagonists significantly reduced mitral/tufted cell excitation of granule cells as measured with extracellular field potentials following antidromic stimulation of the lateral olfactory tract (LOT). In turn, the NMDA antagonists significantly reduced granule cell mediated feedback inhibition of mitral/tufted cells, as measured with field potential recordings of paired-pulse LOT stimulation, suppression of mitral/tufted cell single-unit spontaneous activity following LOT stimulation, and intracellularly recorded IPSP amplitude in mitral/tufted cells following LOT stimulation. While there was not a perfect correlation between the effects of the NMDA antagonists on c-fos mRNA expression and on inhibition, the results suggest that disinhibition of mitral/tufted cells accounts for the observed enhancement in c-fos mRNA expression induced by NMDA receptor antagonists.
嗅球的主要输出神经元，即二尖瓣/簇状细胞，是谷氨酸能的，并通过激活α-氨基-3-羟基-5-甲基-异恶唑-4-丙酸（AMPA）和N-甲基-D-天冬氨酸（NMDA）谷氨酸受体来兴奋抑制性中间神经元，即颗粒细胞。此处呈现的数据表明，原位杂交检测显示，NMDA拮抗剂MK-801和CGP39551能显著增强二尖瓣细胞中c-fos mRNA的表达，但氯胺酮无此作用。在对侧嗅束（LOT）进行逆向刺激后，通过细胞外场电位测量发现，所有这三种拮抗剂均能显著降低二尖瓣/簇状细胞对颗粒细胞的兴奋作用。相应地，通过对成对脉冲LOT刺激进行场电位记录、测量LOT刺激后二尖瓣/簇状细胞单单位自发活动的抑制情况以及细胞内记录LOT刺激后二尖瓣/簇状细胞中的抑制性突触后电位（IPSP）幅度，发现NMDA拮抗剂能显著降低颗粒细胞介导的对二尖瓣/簇状细胞的反馈抑制。虽然NMDA拮抗剂对c-fos mRNA表达的影响与对抑制作用的影响之间并非完全相关，但结果表明，二尖瓣/簇状细胞的去抑制作用可解释NMDA受体拮抗剂诱导的c-fos mRNA表达增强现象。
