Department of Biological Sciences, Columbia University, New York, NY 10027;Department of Neurosciences, Faculty of Medicine, University of Montreal, Montreal, QC, Canada H3C 3J7; and
Department of Biological Sciences, Columbia University, New York, NY 10027;Centre for Neural Circuits and Behaviour, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3SR, United Kingdom.
Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):E2895-904. doi: 10.1073/pnas.1321869111. Epub 2014 Jun 30.
Most excitatory inputs in the mammalian brain are made on dendritic spines, rather than on dendritic shafts. Spines compartmentalize calcium, and this biochemical isolation can underlie input-specific synaptic plasticity, providing a raison d'etre for spines. However, recent results indicate that the spine can experience a membrane potential different from that in the parent dendrite, as though the spine neck electrically isolated the spine. Here we use two-photon calcium imaging of mouse neocortical pyramidal neurons to analyze the correlation between the morphologies of spines activated under minimal synaptic stimulation and the excitatory postsynaptic potentials they generate. We find that excitatory postsynaptic potential amplitudes are inversely correlated with spine neck lengths. Furthermore, a spike timing-dependent plasticity protocol, in which two-photon glutamate uncaging over a spine is paired with postsynaptic spikes, produces rapid shrinkage of the spine neck and concomitant increases in the amplitude of the evoked spine potentials. Using numerical simulations, we explore the parameter regimes for the spine neck resistance and synaptic conductance changes necessary to explain our observations. Our data, directly correlating synaptic and morphological plasticity, imply that long-necked spines have small or negligible somatic voltage contributions, but that, upon synaptic stimulation paired with postsynaptic activity, they can shorten their necks and increase synaptic efficacy, thus changing the input/output gain of pyramidal neurons.
哺乳动物大脑中的大多数兴奋性输入是在树突棘上产生的，而不是在树突干上。树突棘分隔钙，这种生化隔离可以为特定输入的突触可塑性提供基础，为树突棘提供存在的理由。然而，最近的结果表明，树突棘可以经历不同于母树突的膜电位，就好像树突棘颈使树突棘在电学上隔离一样。在这里，我们使用双光子钙成像技术分析了在最小突触刺激下激活的树突棘的形态与它们产生的兴奋性突触后电位之间的相关性。我们发现，兴奋性突触后电位的幅度与树突棘颈的长度呈反比。此外，一种基于尖峰时间的可塑性方案，其中双光子谷氨酸通过一个树突棘进行非光解，并与突触后尖峰配对，会导致树突棘颈的快速收缩，并伴随着诱发树突棘电位幅度的增加。通过数值模拟，我们探讨了解释我们观察结果所需的树突棘颈电阻和突触电导变化的参数范围。我们的数据直接将突触和形态可塑性相关联，这意味着长颈树突棘的体电压贡献较小或可以忽略不计，但在与突触后活动配对的突触刺激下，它们可以缩短树突棘颈并增加突触效能，从而改变锥体细胞的输入/输出增益。
