Department of Psychiatry, Erasmus MC Rotterdam, The Netherlands.
Department of Psychiatry, Erasmus MC Rotterdam, The Netherlands
J Neurosci. 2018 Apr 11;38(15):3631-3642. doi: 10.1523/JNEUROSCI.0074-18.2018. Epub 2018 Mar 5.
Axonal myelination of neocortical pyramidal neurons is modulated dynamically by neuronal activity. Recent studies have shown that a substantial proportion of neocortical myelin content is contributed by fast-spiking, parvalbumin (PV)-positive interneurons. However, it remains unknown whether the myelination of PV interneurons is also modulated by intrinsic activity. Here, we used cell-type-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in adult mice to activate a sparse population of medial prefrontal cortex (mPFC) PV interneurons. Using single-cell axonal reconstructions, we found that DREADD-stimulated PV interneurons exhibited a nearly two-fold increase in total length of myelination, predominantly mediated by a parallel increase of axonal arborization and number of internodes. In contrast, the distribution of axonal interbranch segment distance and myelin internode length were not altered significantly. Topographical analysis revealed that myelination of DREADD-stimulated cells extended to higher axonal branch orders while retaining a similar interbranch distance threshold for myelination. Together, our results demonstrate that chemogenetically induced neuronal activity increases the myelination of neocortical PV interneurons mediated at least in part by an elaboration of their axonal morphology. Myelination is the wrapping of an axon to optimize conduction velocity in an energy-efficient manner. Previous studies have shown that myelination of neocortical pyramidal neurons is experience and activity dependent. We now show that activity-dependent myelin plasticity in the adult neocortex extends to parvalbumin (PV)-expressing fast-spiking interneurons. Chemogenetic stimulation of PV interneurons in the medial prefrontal cortex (mPFC) significantly enhanced axonal myelination, which was paralleled by an increase in axonal arborization. This suggests that activity-dependent axonal plasticity may involve changes in both structural morphology and myelination. Such multicomponent plasticity reveals an unexpected repertoire of anatomical parameters available for optimizing and adapting neuronal networks in response to experience.
皮质锥体神经元的轴突髓鞘形成受到神经元活动的动态调节。最近的研究表明，相当一部分皮质髓鞘含量是由快速放电、副甲状腺素（PV）阳性中间神经元贡献的。然而，PV 中间神经元的髓鞘形成是否也受到内在活动的调节仍然未知。在这里，我们使用成年小鼠中细胞类型特异性的 Designer Receptors Exclusively Activated by Designer Drugs（DREADD）来激活内侧前额叶皮质（mPFC）中稀疏的 PV 中间神经元群体。通过单细胞轴突重建，我们发现 DREADD 刺激的 PV 中间神经元的总髓鞘长度增加了近两倍，主要是通过轴突分支化和节间数的平行增加来介导的。相比之下，轴突分支间段距离和髓鞘节间长度的分布没有显著改变。拓扑分析表明，DREADD 刺激细胞的髓鞘延伸到更高的轴突分支顺序，同时保留了类似的髓鞘化分支间距离阈值。总的来说，我们的结果表明，化学诱导的神经元活动增加了新皮层 PV 中间神经元的髓鞘形成，至少部分是通过其轴突形态的精细调节来介导的。髓鞘形成是一种以节能方式优化轴突传导速度的包裹方式。以前的研究表明，新皮层锥体神经元的髓鞘形成依赖于经验和活动。我们现在表明，成年新皮层中活动依赖性髓鞘可塑性扩展到表达副甲状腺素（PV）的快速放电中间神经元。内侧前额叶皮质（mPFC）中 PV 中间神经元的化学刺激显著增强了轴突髓鞘形成，这与轴突分支化的增加相平行。这表明，活动依赖性轴突可塑性可能涉及结构形态和髓鞘形成的变化。这种多组分可塑性揭示了用于优化和适应神经网络以响应经验的意想不到的解剖学参数库。
