Frontiers in Cellular Neuroscience Cellular Neuroscience at Immature Mossy Fi Bers-ca3 Connections, Activation of Presynaptic Gaba B Receptors by Endogenously Released Gaba Contributes to Synapses Silencing
Frontiers in Cellular Neuroscience Cellular Neuroscience at Immature Mossy Fi Bers-ca3 Connections, Activation of Presynaptic Gaba B Receptors by Endogenously Released Gaba Contributes to Synapses Silencing
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细胞神经科学前沿 未成熟苔藓纤维 Bers-ca3 连接的细胞神经科学，内源性释放的 Gaba 激活突触前 Gaba B 受体有助于突触沉默
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发表时间：
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通讯作者：
E. Cherubini
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文献类型：
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作者：
Victoria F Safi;E. Cherubini
在出生后早期，海马中的相关GABA能活性被认为在突触发生和成年神经元网络的发育中起关键作用。与成年期不同，在这个发育阶段，苔藓纤维（MF）是颗粒细胞的轴突，将GABA释放到CA 3主细胞和中间神经元中。在这里，我们测试的假设，在MF-CA 3连接，GABA B自身受体的紧张性激活是负责释放和突触沉默的低概率。用CGP 55845阻断GABA B受体增加了GABA释放的可能性，并打开了沉默的突触，而用巴氯芬观察到相反的情况。这两种效应都是突触前的，并与成对脉冲比和变异系数的变化有关。此外，通过反复刺激MF或通过阻断GABA转运蛋白GAT-1来增强细胞外GABA浓度，关闭了活跃的突触，这一作用被CGP 55845阻止。在CGP 55845存在下，刺激MF诱导的突触增强。与bumetanide，阳离子-氯离子共转运蛋白NKCC 1的阻滞剂，E GABA从去极化的超极化方向的转变，阻止突触增强，并引起突触抑制，这表明在存在的CGP 55845的情况下观察到的GABA的去极化作用是负责的增强作用。有人提出，GABA从MF末端溢出激活GABA B受体降低了释放的可能性并有助于突触沉默。这将作为一个过滤器，以防止过度激活的自动关联CA 3网络和癫痫发作的出现。与Gi和Go蛋白偶联的受体位于突触前膜和突触后膜上（Bettler等人，2004; Misgeld等人，1995年）。突触后GABA B受体的激活引起内向整流钾通道的开放（Lüscher等人，1997），而突触前GABA B受体的激活主要通过抑制P/Q和N型电压依赖性钙通道引起递质释放的减少（Poncer等，1997年）。虽然突触后GABA B受体受发育调节（Cherubini等人，1998; Gaiarsa等人，1995），突触前GABA B受体在出生时就已存在并发挥功能。已经表明它们控制网络活动（姆克林等人，1996）并调节CA 3主细胞中谷氨酸或GABA介导的突触后电流的幅度（Gaiarsa等，1995年）。然而，这些研究未能确定GABA A介导的突触电流起源于何处。…
Early in postnatal life correlated GABAergic activity in the hippocampus is thought to play a crucial role in synaptogenesis and in the development of adult neuronal networks. Unlike adulthood, at this developmental stage, mossy fi bers (MF) which are the axons of granule cells, release GABA into CA3 principal cells and interneurons. Here, we tested the hypothesis that at MF-CA3 connections, tonic activation of GABA B autoreceptors by GABA is responsible for the low probability of release and synapse silencing. Blocking GABA B receptors with CGP55845 enhanced the probability of GABA release and switched on silent synapses while the opposite was observed with baclofen. Both these effects were presynaptic and were associated with changes in paired-pulse ratio and coeffi cient of variation. In addition, enhancing the extracellular GABA concentration by repetitive stimulation of MF or by blocking the GABA transporter GAT-1, switched off active synapses, an effect that was prevented by CGP55845. In the presence of CGP55845, stimulation of MF-induced synaptic potentiation. The shift of E GABA from the depolarizing to the hyperpolarizing direction with bumetanide, a blocker of the cation-chloride co-transporter NKCC1, prevented synaptic potentiation and caused synaptic depression, suggesting that the depolarizing action of GABA observed in the presence of CGP55845 is responsible for the potentiating effect. It is proposed that, activation of GABA B receptors by spillover of GABA from MF terminals reduces the probability of release and contributes to synapses silencing. This would act as a fi lter to prevent excessive activation of the auto-associative CA3 network and the emergence of seizures. receptors which are coupled to G i and G o proteins are localized on both pre and postsynaptic membranes (Bettler et al., 2004; Misgeld et al., 1995). Activation of postsynaptic GABA B receptors causes the opening of inwardly rectifying potassium channels (Lüscher et al., 1997) whereas activation of presynaptic GABA B receptors causes a reduction in transmitter release mainly via inhibition of P/Q and N types of voltage-dependent calcium channels (Poncer et al., 1997). While postsynaptic GABA B receptors are developmentally regulated (Cherubini et al., 1998; Gaiarsa et al., 1995), presynap-tic GABA B receptors are present and functional already at birth. It has been shown that they control network activity (McLean et al., 1996) and modulate the amplitude of glutamate-or GABA-mediated postsynaptic currents in CA3 principal cells (Gaiarsa et al., 1995). However, these studies failed in identifying where GABA A-mediated synaptic currents originated from. …
DOI：
10.1073/pnas.91.22.10380
发表时间：
1994-10-25
影响因子：
11.1
作者：
ALLEN, C;STEVENS, CF
通讯作者：
STEVENS, CF