Heinbockel Thomas, Laaris Nora, Ennis Matthew
Department of Anatomy, Howard University College of Medicine, 520 W Street NW, Washington, DC 20059, USA.
J Neurophysiol. 2007 Jan;97(1):858-70. doi: 10.1152/jn.00884.2006. Epub 2006 Nov 8.
Main olfactory bulb (MOB) granule cells (GCs) express high levels of the group I metabotropic glutamate receptor (mGluR), mGluR5. We investigated the role of mGluRs in regulating GC activity in rodent MOB slices using whole cell patch-clamp electrophysiology. The group I/II mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD) or the selective group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) depolarized ( approximately 20 mV) and increased the firing rate of GCs. In the presence of ionotropic glutamate and GABA receptor antagonists, DHPG evoked a more modest depolarization ( approximately 8 mV). In voltage clamp, DHPG, but not group II [(2S,2'R,3)-2-(2',3'-dicarboxycyclopropyl)glycine, DCG-IV] or group III [L(+)-2-amino-4-phosphonobutyric acid, L-AP4] mGluR agonists, induced an inward current. The inward current reversed polarity near the potassium equilibrium potential, suggesting mediation by closure of potassium channels. The DHPG-evoked inward current was unaffected by the mGluR1 antagonist (S)-(+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385), was blocked by the group I/II mGluR antagonist (alphaS)-alpha-amino-alpha-[(1S,2S)-2-carboxycyclopropyl]-9H-xanthine-9-propanoic acid (LY341495), and was absent in GCs from mGluR5 knockout mice. LY341495 also attenuated mitral cell-evoked voltage-sensitive dye signals in the external plexiform layer and mitral cell-evoked spikes in GCs. These results suggest that activation of mGluR5 increases GC excitability, an effect that should increase GC-mediated GABAergic inhibition of mitral cells. In support of this: DHPG increased the frequency of spontaneous GABAergic inhibitory postsynaptic currents in mitral cells and LY341495 attenuated the feedback GABAergic postsynaptic potential elicited by intracellular depolarization of mitral cells. Our results suggest that activation of mGluR5 participates in feedforward and/or feedback inhibition at mitral cell to GC dendrodendritic synapses, possibly to modulate lateral inhibition and contrast in the MOB.
主嗅球（MOB）颗粒细胞（GCs）高水平表达I组代谢型谷氨酸受体（mGluR），即mGluR5。我们使用全细胞膜片钳电生理学方法，研究了mGluRs在调节啮齿动物MOB脑片GC活性中的作用。I/II组mGluR激动剂（±）-1-氨基环戊烷-反式-1,3-二羧酸（ACPD）或选择性I组激动剂（RS）-3,5-二羟基苯甘氨酸（DHPG）使GCs去极化（约20 mV）并增加其放电频率。在离子型谷氨酸和GABA受体拮抗剂存在的情况下，DHPG引起的去极化幅度较小（约8 mV）。在电压钳实验中，DHPG可诱导内向电流，而II组[（2S，2'R，3）-2-（2'，3'-二羧基环丙基）甘氨酸，DCG-IV]或III组[L（+）-2-氨基-4-膦酰丁酸，L-AP4] mGluR激动剂则不能。内向电流在钾平衡电位附近反转极性，提示其由钾通道关闭介导。DHPG诱发的内向电流不受mGluR1拮抗剂（S）-（+）-α-氨基-4-羧基-2-甲基苯乙酸（LY367385）的影响，但可被I/II组mGluR拮抗剂（αS）-α-氨基-α-[（1S，2S）-2-羧基环丙基]-9H-黄嘌呤-9-丙酸（LY341495）阻断，且在mGluR5基因敲除小鼠的GCs中不存在。LY341495还减弱了外丛状层中僧帽细胞诱发的电压敏感染料信号以及GCs中僧帽细胞诱发的动作电位。这些结果表明，mGluR5的激活增加了GC的兴奋性，这种作用应会增强GC介导的对僧帽细胞的GABA能抑制。支持这一观点的证据如下：DHPG增加了僧帽细胞中自发性GABA能抑制性突触后电流的频率，而LY341495减弱了僧帽细胞细胞内去极化诱发的反馈性GABA能突触后电位。我们的结果表明，mGluR5的激活参与了从僧帽细胞到GC树-树突触的前馈和/或反馈抑制，可能是为了调节MOB中的侧向抑制和对比度。
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