Inhibitory control of LTP and LTD: Stability of synapse strength
Inhibitory control of LTP and LTD: Stability of synapse strength
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DOI：
10.1152/jn.1999.81.4.1559
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发表时间：
1999-04-01
影响因子：
2.5
通讯作者：
Mauk, MD
中科院分区：
文献类型：
--
作者：
Steele, PM;Mauk, MD
虽然关于突触可塑性的诱导已经知道很多，但记忆的持久性表明了解维持突触强度和防止不必要的突触变化的因素的重要性。在这里，我们提出证据表明，海马区CA1区反复出现的抑制性连接可能通过调节诱导长时程增强和抑制的相对能力(LTP和LTD)来参与这一任务。在海马片上应用γ-氨基丁酸(GABA)A型激动剂蝇草酚可增加产生LTD的频率范围，而在有A型GABA拮抗剂的情况下，仅在很低的刺激频率(0.25-0.5赫兹)下才能诱导产生LTD。由于GABA能传入CA1区锥体细胞的来源之一是通过反复抑制，因此我们检验了突触后峰活动增加将增加反馈GABA抑制并有利于LTD的诱导的预测。通过使用8赫兹的诱导刺激，单独使用不会对突触强度产生净变化的刺激，我们发现刺激出现在锥体细胞棘波的逆行激活过程中。这种作用被印防己毒素阻断。反复抑制对LTP和LTD的影响显示出可能降低突触强度自我加强和失控变化的可能性。这种机制可能有助于维持突触强度的模式，尽管突触激活产生了持续的可塑性机会。
Although much is known about the induction of synaptic plasticity, the persistence of memories suggests the importance of understanding factors that maintain synaptic strength and prevent unwanted synaptic changes. Here we present evidence that recurrent inhibitory connections in the CA1 region of hippocampus may contribute to this task by modulating the relative ability to induce long-term potentiation and depression (LTP and LTD). Bath application of the gamma-aminobutyric acid (GABA) type A agonist muscimol to hippocampal slices increased the range of frequencies that produce LTD, whereas in the presence of the GABA type A antagonist picrotoxin LTD was induced only at very low stimulation frequencies (0.25-0.5 Hz). Because one source of GABAergic input to CAI pyramidal cells is via recurrent inhibition, we tested the prediction that elevated postsynaptic spike activity would increase feedback GABA inhibition and favor the induction of LTD. By using an induction stimulation of 8 Hz, which alone produced no net change in synaptic strength, we found that stimulation presented during antidromic activation of pyramidal cell spikes induced LTD. This effect was blocked by picrotoxin. The influence of recurrent inhibition on LTP and LTD displays properties that may decrease the potential for self-reinforcing, runaway changes in synapse strength. A mechanism of this sort may help maintain patterns of synaptic strengths despite the ongoing opportunities for plasticity produced by synapse activation.