Mossy fiber-evoked subthreshold responses induce timing-dependent plasticity at hippocampal CA3 recurrent synapses
Mossy fiber-evoked subthreshold responses induce timing-dependent plasticity at hippocampal CA3 recurrent synapses
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DOI：
10.1073/pnas.1317667111
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发表时间：
2014-03-18
影响因子：
11.1
通讯作者：
Gerber, Urs
中科院分区：
文献类型：
--
作者：
Brandalise, Federico;Gerber, Urs
齿状颗粒细胞在靶向CA3锥体细胞中表现出异常低的活性，并且很少诱发动作电位。因此，尚不清楚颗粒细胞的这种弱输入如何维持靶向CA3网络中足够水平的突触可塑性。我们报道苔藓纤维诱发的阈值下电位足以诱导CA3锥体细胞之间的突触可塑性，从而补充稀疏动作电位放电。CA3-CA3复发性突触反应与随后的阈值下苔藓纤维反应的重复配对在体外诱导了大鼠海马CA3复发性突触的长时程增强。反转输入的时间会导致长期的抑郁。其潜在机制依赖于苔藓纤维诱发的被动传导的巨大兴奋性突触后电位，该电位通过解除镁阻滞剂而增强活跃的CA3复发突触的NMDA受体介导的电流。由此产生的NMDA峰产生超线性去极化，有助于与记忆有关的海马神经元团的突触可塑性。
Dentate granule cells exhibit exceptionally low levels of activity and rarely elicit action potentials in targeted CA3 pyramidal cells. It is thus unclear how such weak input from the granule cells sustains adequate levels of synaptic plasticity in the targeted CA3 network. We report that subthreshold potentials evoked by mossy fibers are sufficient to induce synaptic plasticity between CA3 pyramidal cells, thereby complementing the sparse action potential discharge. Repetitive pairing of a CA3-CA3 recurrent synaptic response with a subsequent subthreshold mossy fiber response induced long-term potentiation at CA3 recurrent synapses in rat hippocampus in vitro. Reversing the timing of the inputs induced long-term depression. The underlying mechanism depends on a passively conducted giant excitatory postsynaptic potential evoked by a mossy fiber that enhances NMDA receptor-mediated current at active CA3 recurrent synapses by relieving magnesium block. The resulting NMDA spike generates a supralinear depolarization that contributes to synaptic plasticity in hippocampal neuronal ensembles implicated in memory.