Graupner Michael, Wallisch Pascal, Ostojic Srdjan
Center for Neural Science, New York University, New York, New York 10003,
Laboratoire de Physiologie Cérébrale-UMR 8118, CNRS, Université Paris Descartes, 75270 Paris Cedex 06, France, and.
J Neurosci. 2016 Nov 2;36(44):11238-11258. doi: 10.1523/JNEUROSCI.0104-16.2016.
Synaptic plasticity is sensitive to the rate and the timing of presynaptic and postsynaptic action potentials. In experimental protocols inducing plasticity, the imposed spike trains are typically regular and the relative timing between every presynaptic and postsynaptic spike is fixed. This is at odds with firing patterns observed in the cortex of intact animals, where cells fire irregularly and the timing between presynaptic and postsynaptic spikes varies. To investigate synaptic changes elicited by in vivo-like firing, we used numerical simulations and mathematical analysis of synaptic plasticity models. We found that the influence of spike timing on plasticity is weaker than expected from regular stimulation protocols. Moreover, when neurons fire irregularly, synaptic changes induced by precise spike timing can be equivalently induced by a modest firing rate variation. Our findings bridge the gap between existing results on synaptic plasticity and plasticity occurring in vivo, and challenge the dominant role of spike timing in plasticity.
Synaptic plasticity, the change in efficacy of connections between neurons, is thought to underlie learning and memory. The dominant paradigm posits that the precise timing of neural action potentials (APs) is central for plasticity induction. This concept is based on experiments using highly regular and stereotyped patterns of APs, in stark contrast with natural neuronal activity. Using synaptic plasticity models, we investigated how irregular, in vivo-like activity shapes synaptic plasticity. We found that synaptic changes induced by precise timing of APs are much weaker than suggested by regular stimulation protocols, and can be equivalently induced by modest variations of the AP rate alone. Our results call into question the dominant role of precise AP timing for plasticity in natural conditions.
突触可塑性对突触前和突触后动作电位的频率和时间敏感。在诱导可塑性的实验方案中，施加的尖峰序列通常是规则的，并且每个突触前和突触后尖峰之间的相对时间是固定的。这与在完整动物皮层中观察到的放电模式不一致，在完整动物皮层中，细胞不规则放电，突触前和突触后尖峰之间的时间各不相同。为了研究类似体内放电引发的突触变化，我们对突触可塑性模型进行了数值模拟和数学分析。我们发现，尖峰时间对可塑性的影响比常规刺激方案预期的要弱。此外，当神经元不规则放电时，精确尖峰时间诱导的突触变化可以由适度的放电频率变化等效诱导。我们的研究结果弥合了现有突触可塑性研究结果与体内发生的可塑性之间的差距，并挑战了尖峰时间在可塑性中的主导作用。
突触可塑性，即神经元之间连接效能的变化，被认为是学习和记忆的基础。主导范式认为，神经动作电位（AP）的精确时间对于可塑性诱导至关重要。这一概念基于使用高度规则和刻板的AP模式的实验，这与自然神经元活动形成鲜明对比。我们使用突触可塑性模型，研究了不规则的、类似体内的活动如何塑造突触可塑性。我们发现，AP精确时间诱导的突触变化比常规刺激方案所暗示的要弱得多，并且仅由AP频率的适度变化就可以等效诱导。我们的结果质疑了精确AP时间在自然条件下对可塑性的主导作用。
