Metabotropic glutamate receptors in the main olfactory bulb drive granule cell-mediated inhibition
Metabotropic glutamate receptors in the main olfactory bulb drive granule cell-mediated inhibition
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DOI：
10.1152/jn.00884.2006
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发表时间：
2007-01-01
影响因子：
2.5
通讯作者：
Ennis, Matthew
中科院分区：
文献类型：
--
作者：
Heinbockel, Thomas;Laaris, Nora;Ennis, Matthew
主嗅球中的代谢型谷氨酸受体驱动颗粒细胞介导的抑制。J Neurophysiol 97：858-870，2007. 2006年11月8日首次出版; doi：10.1152/jn. 00884.2006.主嗅球（MOB）颗粒细胞（GC）表达高水平的第一组代谢型谷氨酸受体（mGluR），mGluR 5。我们使用全细胞膜片钳电生理学研究了mGluRs在调节啮齿动物MOB切片中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）去极化（类似于20 mV）并增加GC的放电速率。在离子型谷氨酸和GABA受体拮抗剂的存在下，DHPG引起更温和的去极化（类似于8 mV）。在电压钳中，DHPG而不是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-膦酰基丁酸，L-AP 4] mGluR激动剂诱导内向电流。内向电流在钾平衡电位附近反转极性，表明通过关闭钾通道进行调解。DHPG诱发的内向电流不受mGluR 1拮抗剂（S）-（+）-α-氨基-4-羧基-2-甲基苯乙酸（LY 367385）的影响，被I/II组mGluR拮抗剂（α S）-α-氨基-α [（1 S，2S）-2-羧基环丙基]-9H-黄嘌呤-9-丙酸（LY 341495）阻断，并且在mGluR 5敲除小鼠的GC中不存在。LY 341495还减弱了外网状层中的二尖瓣细胞诱发的电压敏感染料信号和GC中的二尖瓣细胞诱发的尖峰。这些结果表明mGluR 5的激活增加GC兴奋性，这种作用应该增加GC介导的GABA能抑制二尖瓣细胞。为此：DHPG增加二尖瓣细胞自发性GABA能抑制性突触后电流的频率，LY 341495减弱二尖瓣细胞内去极化引起的反馈性GABA能突触后电位。我们的研究结果表明，激活mGluR 5参与前馈和/或反馈抑制在二尖瓣细胞GC树-树突触，可能是调制侧抑制和对比度的MOB。
Metabotropic glutamate receptors in the main olfactory bulb drive granule cell-mediated inhibition. J Neurophysiol 97: 858-870, 2007. First published November 8, 2006; doi:10.1152/jn. 00884.2006. 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 patchclamp electrophysiology. The group I/II mGluR agonist (+/-)-1-aminocyclopentanetrans- 1,3-dicarboxylic acid (ACPD) or the selective group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) depolarized (similar to 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 (similar to 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 (alpha S)-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.