Dopaminergic modulation of neuroplasticity: mechanistic aspects, and transferability to prefrontal functions

神经可塑性的多巴胺能调节：机制方面和前额叶功能的可转移性

• 批准号: 454812028
• 负责人: Professor Dr. Michael A. Nitsche
• 金额: --
• 依托单位: Projektgruppe Neuromodulation
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/454812028?language=en
• 关键词: Dopaminergic; modulation; neuroplasticity; mechanistic; aspects

As one of the most important neuromodulators in the brain, dopamine plays a key role in many neural and cognitive functions such as learning and memory. It is also involved in many neurological and psychiatric diseases. The neurophysiological basis of these effects is suggested to be the modulatory effect of dopamine on neural excitability and plasticity, which has been intensively investigated in animal models. It has been proposed that dopamine facilitates learning via enhancing the signal-to-noise ratio of neural network activity, as a result of the balance between distinct regulations of dopaminergic receptor subtypes, particularly D1 and D2. In the previous funding period we have shown such a ‘focusing’ effect of dopamine, both receptor subtype- and dose-dependent, on motor cortical plasticity in healthy humans. In this proposed project, we aim to continue exploring the underlying mechanisms. First, the impact of glutamatergic and GABAergic mechanisms on the dopaminergic impact on plasticity will be investigated, as these have been shown to be prominently and antagonistically altered by dopamine receptor subtype activity. We will furthermore explore specifically the mechanistic basis for the focusing effect of DA on plasticity. Finally, we will explore if, and to which degree, the results obtained in the motor cortex model can be transferred to the prefrontal cortex, which shows gradually different DA receptor compositions, and plays a prominent role in diverse cognitive functions. The results will help us to gain detailed insight in the mechanisms of dopaminergic effects on neuroplasticity of the human brain, and its relevance for cognition.

多巴胺作为脑内最重要的神经调质之一，在学习和记忆等许多神经和认知功能中起着关键作用。它还涉及许多神经和精神疾病。这些作用的神经生理学基础被认为是多巴胺对神经兴奋性和可塑性的调节作用，这已经在动物模型中得到了深入的研究。已经提出多巴胺通过增强神经网络活动的信噪比来促进学习，这是由于多巴胺能受体亚型（特别是D1和D2）的不同调节之间的平衡。在之前的资助期间，我们已经证明了多巴胺对健康人运动皮层可塑性的这种“聚焦”效应，既有受体亚型依赖性，也有剂量依赖性。在这个拟议的项目中，我们的目标是继续探索潜在的机制。首先，将研究多巴胺能和GABA能机制对多巴胺能可塑性影响的影响，因为这些机制已被多巴胺受体亚型活性显着和拮抗性改变。我们将进一步探讨DA对可塑性的聚焦效应的机制基础。最后，我们将探讨在运动皮层模型中获得的结果是否以及在多大程度上可以转移到前额叶皮层，前额叶皮层逐渐显示出不同的DA受体组成，并在各种认知功能中发挥重要作用。这些结果将有助于我们深入了解多巴胺能对人脑神经可塑性的作用机制及其与认知的相关性。