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海马苔藓纤维-中间神经元突触处的长时程增强和长时程抑制

PTP and LTP at a hippocampal mossy fiber-interneuron synapse.

作者信息

Alle H, Jonas P, Geiger J R

机构信息

Physiologisches Institut der Universität Freiburg, D-79104 Freiburg, Germany.

出版信息

Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14708-13. doi: 10.1073/pnas.251610898.

Abstract

The mossy fiber-CA3 pyramidal neuron synapse is a main component of the hippocampal trisynaptic circuitry. Recent studies, however, suggested that inhibitory interneurons are the major targets of the mossy fiber system. To study the regulation of mossy fiber-interneuron excitation, we examined unitary and compound excitatory postsynaptic currents in dentate gyrus basket cells, evoked by paired recording between granule and basket cells or extracellular stimulation of mossy fiber collaterals. The application of an associative high-frequency stimulation paradigm induced posttetanic potentiation (PTP) followed by homosynaptic long-term potentiation (LTP). Analysis of numbers of failures, coefficient of variation, and paired-pulse modulation indicated that both PTP and LTP were expressed presynaptically. The Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) did not affect PTP or LTP at a concentration of 10 mM but attenuated LTP at a concentration of 30 mM. Both forskolin, an adenylyl cyclase activator, and phorbolester diacetate, a protein kinase C stimulator, lead to a long-lasting increase in excitatory postsynaptic current amplitude. H-89, a protein kinase A inhibitor, and bisindolylmaleimide, a protein kinase C antagonist, reduced PTP, whereas only bisindolylmaleimide reduced LTP. These results may suggest a differential contribution of protein kinase A and C pathways to mossy fiber-interneuron plasticity. Interneuron PTP and LTP may provide mechanisms to maintain the balance between synaptic excitation of interneurons and that of principal neurons in the dentate gyrus-CA3 network.

摘要

苔藓纤维-CA3锥体细胞神经元突触是海马三突触回路的主要组成部分。然而,最近的研究表明,抑制性中间神经元是苔藓纤维系统的主要靶点。为了研究苔藓纤维-中间神经元兴奋的调节,我们通过颗粒细胞与篮状细胞之间的配对记录或苔藓纤维侧支的细胞外刺激,检测了齿状回篮状细胞中的单突触和复合兴奋性突触后电流。应用联合高频刺激范式可诱导强直后增强(PTP),随后是同突触长时程增强(LTP)。对失败次数、变异系数和双脉冲调制的分析表明,PTP和LTP均在突触前表达。Ca(2+)螯合剂1,2-双(2-氨基苯氧基)乙烷-N,N,N',N'-四乙酸(BAPTA)在10 mM浓度时不影响PTP或LTP,但在30 mM浓度时减弱LTP。腺苷酸环化酶激活剂福斯高林和蛋白激酶C刺激剂佛波酯二乙酸酯均可导致兴奋性突触后电流幅度的持久增加。蛋白激酶A抑制剂H-89和蛋白激酶C拮抗剂双吲哚马来酰亚胺可降低PTP,而只有双吲哚马来酰亚胺可降低LTP。这些结果可能提示蛋白激酶A和C通路对苔藓纤维-中间神经元可塑性的不同贡献。中间神经元的PTP和LTP可能提供维持齿状回-CA3网络中中间神经元与主神经元突触兴奋之间平衡的机制。

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