Postsynaptic response to stimulation of the Schaffer collaterals with properties similar to those of synaptosomal aspartate release.
Postsynaptic response to stimulation of the Schaffer collaterals with properties similar to those of synaptosomal aspartate release.
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DOI：
10.1016/j.brainres.2009.07.104
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发表时间：
2009-10-27
期刊：
影响因子：
2.9
通讯作者：
Nadler, J. Victor
中科院分区：
文献类型：
--
作者：
Zhang, Xuying;Nadler, J. Victor
天冬氨酸满足识别中枢神经递质通常需要的所有标准。然而，很少有电生理学证据支持天冬氨酸传输的存在。在对大鼠海马突触体的研究中，化学诱发的天冬氨酸释放与谷氨酸释放在突触前活性区外Ca2+浓度增加的相对敏感性、与P/ q型Ca2+通道的低效偶联、对KB-R7943的敏感性以及对天然梭状菌毒素的抗性方面存在差异。我们利用这些差异在器官型海马切片培养中寻找潜在的天门冬氨酸介导的Schaffer侧突触反应。切片培养用肉毒杆菌神经毒素C （BoNT/C）预处理，以消除大部分谷氨酸释放，从而可以通过全细胞膜片钳记录检测到化合物EPSC中较小的天冬氨酸样成分。在对照培养中，NMDA受体激活仅占诱发EPSC的18%，nr2b选择性拮抗剂仅减少了20%的NMDA受体介导成分。阻断P/ q型Ca2+通道基本消除了响应，0.1 μM KB-R7943没有显著影响。然而，在BoNT/ c预处理培养中，NMDA受体激活占诱发EPSC的77%，nr2b选择性拮抗剂将NMDA受体介导的成分减少了57%。阻断P/ q型Ca2+通道仅使响应降低28%，而0.1 μM KB-R7943使响应降低45%。这些结果表明，部分Schaffer侧枝突触反应具有类似于突触体释放天冬氨酸的药理特性，因此可能至少部分由释放的天冬氨酸介导。
Aspartate satisfies all the criteria normally required for identification of a CNS neurotransmitter. Nevertheless, little electrophysiological evidence supports the existence of aspartate transmission. In studies with rat hippocampal synaptosomes, chemically-evoked aspartate release differed from glutamate release in its relative sensitivity to increased Ca2+ concentration outside the presynaptic active zones, inefficient coupling to P/Q-type Ca2+ channels, sensitivity to KB-R7943, and resistance to native Clostridial toxins. We took advantage of these differences to search for a potential aspartate-mediated response at Schaffer collateral synapses in organotypic hippocampal slice cultures. The slice cultures were pretreated with botulinum neurotoxin C (BoNT/C) to eliminate most of the glutamate release so that an expectedly smaller aspartate-like component of the compound EPSC could be detected by whole cell patch clamp recording. In control cultures, NMDA receptor activation accounted for only 18% of the evoked EPSC and an NR2B-selective antagonist reduced the NMDA receptor-mediated component by only 20%. Block of P/Q-type Ca2+ channels essentially eliminated the response and 0.1 μM KB-R7943 had no significant effect. In BoNT/C-pretreated cultures, however, NMDA receptor activation accounted for 77% of the evoked EPSC and an NR2B-selective antagonist reduced the NMDA receptor-mediated component by 57%. Block of P/Q-type Ca2+ channels reduced the response by only 28%, but 0.1 μM KB-R7943 reduced it by 45%. These results suggest that part of the Schaffer collateral synaptic response has pharmacological properties similar to those of synaptosomal aspartate release and may therefore be mediated at least partly by released aspartate.
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DOI：
10.1083/jcb.200406126
发表时间：
2005-02-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Berliocchi L;Fava E;Leist M;Horvat V;Dinsdale D;Read D;Nicotera P
通讯作者：
Nicotera P
影响因子：
5
作者：
Liang, Guo Hua;Kim, Ji Aee;Suh, Suk Hyo
通讯作者：
Suh, Suk Hyo
影响因子：
56.9
作者：
Lledo, PM;Zhang, XY;Nicoll, RA
通讯作者：
Nicoll, RA
影响因子：
4.8
作者：
Iwamoto, T;Watano, T;Shigekawa, M
通讯作者：
Shigekawa, M
影响因子：
4.7
作者：
BURKE, SP;NADLER, JV
通讯作者：
NADLER, JV