Letzkus Johannes J, Kampa Björn M, Stuart Greg J
Division of Neuroscience, The John Curtin School of Medical Research, Australian National University, Canberra ACT 0200, Australia.
J Neurosci. 2006 Oct 11;26(41):10420-9. doi: 10.1523/JNEUROSCI.2650-06.2006.
Previous studies focusing on the temporal rules governing changes in synaptic strength during spike timing-dependent synaptic plasticity (STDP) have paid little attention to the fact that synaptic inputs are distributed across complex dendritic trees. During STDP, propagation of action potentials (APs) back to the site of synaptic input is thought to trigger plasticity. However, in pyramidal neurons, backpropagation of single APs is decremental, whereas high-frequency bursts lead to generation of distal dendritic calcium spikes. This raises the question whether STDP learning rules depend on synapse location and firing mode. Here, we investigate this issue at synapses between layer 2/3 and layer 5 pyramidal neurons in somatosensory cortex. We find that low-frequency pairing of single APs at positive times leads to a distance-dependent shift to long-term depression (LTD) at distal inputs. At proximal sites, this LTD could be converted to long-term potentiation (LTP) by dendritic depolarizations suprathreshold for BAC-firing or by high-frequency AP bursts. During AP bursts, we observed a progressive, distance-dependent shift in the timing requirements for induction of LTP and LTD, such that distal synapses display novel timing rules: they potentiate when inputs are activated after burst onset (negative timing) but depress when activated before burst onset (positive timing). These findings could be explained by distance-dependent differences in the underlying dendritic voltage waveforms driving NMDA receptor activation during STDP induction. Our results suggest that synapse location within the dendritic tree is a crucial determinant of STDP, and that synapses undergo plasticity according to local rather than global learning rules.
以往聚焦于尖峰时间依赖型突触可塑性（STDP）期间突触强度变化的时间规则的研究，很少关注突触输入分布在复杂树突树上这一事实。在STDP过程中，动作电位（AP）向突触输入位点的反向传播被认为会触发可塑性。然而，在锥体神经元中，单个AP的反向传播是递减的，而高频爆发会导致远端树突钙峰的产生。这就提出了一个问题，即STDP学习规则是否取决于突触位置和放电模式。在这里，我们在体感皮层第2/3层和第5层锥体神经元之间的突触处研究了这个问题。我们发现，在正时单个AP的低频配对会导致远端输入处向长时程抑制（LTD）的距离依赖性转变。在近端位点，这种LTD可以通过高于阈值的树突去极化以进行BAC放电或通过高频AP爆发转化为长时程增强（LTP）。在AP爆发期间，我们观察到LTP和LTD诱导的时间要求存在渐进的、距离依赖性的转变，使得远端突触表现出新颖的时间规则：当输入在爆发开始后被激活时（负时）它们增强，但在爆发开始前被激活时（正时）它们抑制。这些发现可以通过STDP诱导期间驱动NMDA受体激活的潜在树突电压波形的距离依赖性差异来解释。我们的结果表明，树突树内的突触位置是STDP的关键决定因素，并且突触根据局部而非全局学习规则进行可塑性变化。
