Evidence for Tonic Control by the GABAA Receptor of Extracellular D-Serine Concentrations in the Medial Prefrontal Cortex of Rodents
Evidence for Tonic Control by the GABAA Receptor of Extracellular D-Serine Concentrations in the Medial Prefrontal Cortex of Rodents
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啮齿类动物内侧前额皮质细胞外 D-丝氨酸浓度的 GABAA 受体强直控制的证据
DOI：
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发表时间：
2017
影响因子：
4.8
通讯作者：
T. Nishikawa
中科院分区：
文献类型：
--
作者：
A. Umino;Sayuri Ishiwata;H. Iwama;T. Nishikawa
内源性D-丝氨酸是哺乳动物前脑N-甲基-D-天冬氨酸谷氨酸受体（NMDAR）的一种显性共激动剂。虽然NMDAR通过与各种神经递质系统相互作用来调节高级脑功能，但D-丝氨酸与超神经递质系统之间可能的相互作用在很大程度上仍然是难以捉摸的。对于第一次，我们表明在大鼠和小鼠使用体内微透析技术，细胞外的D-丝氨酸浓度下紧张性增加控制的主要抑制性递质，GABA，通过GABAA（GABAAR）在内侧前额叶皮层（mPFC）。因此，选择性GABAAR拮抗剂荷包牡丹碱（BIC）的mPFC内输注引起大鼠mPFC中D-丝氨酸细胞外水平的浓度依赖性和可逆性降低，而不影响另一种内在NMDAR促凝剂甘氨酸和NMDAR激动剂L-谷氨酸的水平。BIC的降低作用通过共输注选择性GABAA激动剂蝇蕈醇（MUS）消除，并通过GABAA拮抗剂gabazine（GBZ）模拟。相比之下，分别用萨氯芬或（1，2，5，6-四氢吡啶-4-基）-甲基次膦酸（TPMPA）选择性阻断GABAB或同聚体ρGABAA（以前称为GABAC）受体，未能下调前额细胞外D-丝氨酸水平。此外，局部BIC应用减弱了给予mPFC的NMDA增加皮质细胞外牛磺酸浓度的能力，表明NMDAR功能减退。最后，在小鼠mPFC中，通过将BIC局部注射到前额叶部分来减少细胞外D-丝氨酸水平，并且通过分别与河豚毒素（TTX）或氟柠檬酸盐（Fluo）共局部注射来抑制神经元或神经胶质活性来排除。这些发现表明，GABAAR介导的调节的D-丝氨酸信号可能发挥微调的NMDAR功能，并需要在哺乳动物mPFC的神经元和胶质细胞的活动。
Endogenous D-serine is a putative dominant co-agonist for the N-methyl-D-aspartate glutamate receptor (NMDAR) in the mammalian forebrain. Although the NMDAR regulates the higher order brain functions by interacting with various neurotransmitter systems, the possible interactions between D-serine and an extra-glutamatergic system largely remain elusive. For the first time, we show in the rat and mouse using an in vivo microdialysis technique that the extracellular D-serine concentrations are under tonic increasing control by a major inhibitory transmitter, GABA, via the GABAA (GABAAR) in the medial prefrontal cortex (mPFC). Thus, an intra-mPFC infusion of a selective GABAAR antagonist, bicuculline (BIC), caused a concentration-dependent and reversible decrease in the extracellular levels of D-serine in the rat mPFC without affecting those of another intrinsic NMDAR coagonist, glycine and an NMDAR agonist, L-glutamate. The decreasing effects of BIC were eliminated by co-infusion of a selective GABAA agonist, muscimol (MUS) and were mimicked by a GABAA antagonist, gabazine (GBZ). In contrast, selective blockade of the GABAB or homomeric ρGABAA (formerly GABAC) receptor by saclofen or (1,2,5,6-tetrahydropyridin-4-yl)-methylphosphinic acid (TPMPA), respectively, failed to downregulate the prefrontal extracellular D-serine levels. Moreover, the local BIC application attenuated the ability of NMDA given to the mPFC to increase the cortical extracellular concentrations of taurine, indicating the hypofunction of the NMDAR. Finally, in the mouse mPFC, the reduction of the extracellular D-serine levels by a local injection of BIC into the prefrontal portion was replicated, and was precluded by inhibition of the neuronal or glial activity by co-local injection with tetrodotoxin (TTX) or fluorocitrate (Fluo), respectively. These findings suggest that the GABAAR-mediated regulation of the D-serine signaling may exert fine-tuning of the NMDAR function and require both neuronal and glial activities in the mammalian mPFC.
影响因子：
13.8
作者：
Ogden KK;Traynelis SF
通讯作者：
Traynelis SF
DOI：
10.1073/pnas.97.9.4926
发表时间：
2000-04-25
影响因子：
11.1
作者：
Mothet, JP;Parent, AT;Snyder, SH
通讯作者：
Snyder, SH