Department of Molecular Neurobiology, Max-Planck-Institute for Medical Research, 69120 Heidelberg, Germany.
J Physiol. 2010 Nov 15;588(Pt 22):4475-88. doi: 10.1113/jphysiol.2010.198366. Epub 2010 Sep 27.
Synaptic plasticity of different inputs converging onto CA3 pyramidal neurons is central to theories of hippocampal function. The mossy fibre (MF) input to these neurons is thought to exhibit plasticity that is in nearly all aspects fundamentally different from plasticity in other brain regions: in particular, when induced by high frequency presynaptic stimulation, plasticity at these synapses is independent of NMDA receptor (NMDAR) activation and presynaptically expressed. Here, we show that different stimulation protocols that depend on the close timing of MF activity and postsynaptic spikes induce bidirectional plasticity in CA3 neurons in 3-week-old rats. Long-term potentiation (LTP) is observed when an excitatory postsynaptic potential (EPSP), evoked by MF stimulation, precedes a single postsynaptic action potential (AP) or a brief AP burst by 10 ms. Instead, timing-dependent long-term depression (LTD) requires the pairing of a single AP to an EPSP with a delay of 30 ms. The pairing of APs to synaptic activity is required for plasticity induction, since the application of unpaired APs or EPSPs did not alter synaptic strength. Furthermore, our results demonstrate that both timing-dependent LTP and LTD critically depend on the activation of NMDARs. Specifically blocking postsynaptic NMDARs prevents plasticity, demonstrating that NMDARs important to spike-timing-dependent plasticity in CA3 neurons are required at postsynaptic sites. In summary, this study shows that the close timing of APs to MF excitatory synaptic input can alter synaptic efficacy in CA3 neurons in a bidirectional manner.
不同传入信号在 CA3 锥体神经元上的突触可塑性是海马体功能理论的核心。这些神经元的苔藓纤维（MF）输入被认为表现出几乎在所有方面都与其他脑区的可塑性根本不同的可塑性：特别是，当通过高频突触前刺激诱导时，这些突触的可塑性与 NMDA 受体（NMDAR）的激活和突触前表达无关。在这里，我们表明，依赖于 MF 活动和突触后尖峰的紧密时间关系的不同刺激方案在 3 周龄大鼠的 CA3 神经元中诱导双向可塑性。当由 MF 刺激引发的兴奋性突触后电位（EPSP）在前一个突触后动作电位（AP）或短暂的 AP 爆发之前提前 10ms 时，观察到长时程增强（LTP）。相反，依赖时间的长时程抑制（LTD）需要将单个 AP 与 EPSP 配对，延迟 30ms。AP 与突触活动的配对是诱导可塑性所必需的，因为未配对的 AP 或 EPSP 的应用不会改变突触强度。此外，我们的结果表明，依赖时间的 LTP 和 LTD 都严重依赖于 NMDAR 的激活。具体来说，阻断突触后 NMDAR 可防止可塑性，表明在 CA3 神经元中对尖峰时间依赖性可塑性很重要的 NMDAR 是在突触后部位需要的。总之，这项研究表明，AP 与 MF 兴奋性突触输入的紧密时间关系可以以双向方式改变 CA3 神经元的突触效能。
