Lindroos Robert, Hellgren Kotaleski Jeanette
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Science for Life Laboratory, Department of Computational Science and Technology, The Royal Institute of Technology, Stockholm, Sweden.
Eur J Neurosci. 2021 Apr;53(7):2117-2134. doi: 10.1111/ejn.14891. Epub 2020 Aug 1.
The input structure of the basal ganglia, striatum, receives dense neuromodulatory input in the form of dopamine and acetylcholine. The two systems are tightly connected, for example, synchronized activity of cholinergic interneurons, leading to increased acetylcholine release, has been shown to directly trigger dopamine release from dopaminergic terminals in striatum. Both signals are further needed for induction of locomotion. High dopamine concentration leads to increased excitability of the direct pathway striatal projection neurons. High cholinergic tone inhibits various potassium channels further increasing the excitability of striatal projection neurons. Here, we investigate the combined effect of concurrent high acetylcholine and dopamine using biophysically detailed models based on rodent data. The aim of the study is to investigate how neuromodulation affects dendritic integration. The result shows that neuromodulation paired with synaptic activation of dendrites can give rise to complex spiking patterns, resembling spike shapes seen in the hippocampus. In the hippocampus, these complex spikes are associated with behavioral time scale plasticity and place cell tuning. We further investigate the mechanisms behind the complex spikes and find that there are two components, one axo-somatic and one dendritic in origin.
基底神经节的输入结构——纹状体，以多巴胺和乙酰胆碱的形式接受密集的神经调质输入。这两个系统紧密相连，例如，胆碱能中间神经元的同步活动会导致乙酰胆碱释放增加，已被证明能直接触发纹状体中多巴胺能终末释放多巴胺。这两种信号对于运动的诱导也是必需的。高多巴胺浓度会导致直接通路纹状体投射神经元的兴奋性增加。高胆碱能张力会抑制各种钾通道，进一步增加纹状体投射神经元的兴奋性。在此，我们使用基于啮齿动物数据的生物物理详细模型，研究高乙酰胆碱和多巴胺同时存在时的联合效应。该研究的目的是探究神经调质如何影响树突整合。结果表明，神经调质与树突的突触激活相结合可产生复杂的尖峰模式，类似于在海马体中看到的尖峰形状。在海马体中，这些复杂尖峰与行为时间尺度可塑性和位置细胞调谐有关。我们进一步研究了复杂尖峰背后的机制，发现有两个成分，一个起源于轴突-胞体，另一个起源于树突。
