University Pierre and Marie Curie, Paris, France.
J Neurosci. 2013 Aug 21;33(34):13914-26. doi: 10.1523/JNEUROSCI.0466-13.2013.
Long-term memory in the prefrontal cortex is a necessary component of adaptive executive control and is strongly modulated by dopamine. However, the functional significance of this dopaminergic modulation remains elusive. In vitro experimental results on dopamine-dependent shaping of prefrontal long-term plasticity often appear inconsistent and, altogether, draw a complicated picture. It is also generally difficult to relate these findings to in vivo observations given strong differences between the two experimental conditions. This study presents a unified view of the functional role of dopamine in the prefrontal cortex by framing it within the Bienenstock-Cooper-Munro theory of cortical plasticity. We investigate dopaminergic modulation of long-term plasticity through a multicompartment Hodgkin-Huxley model of a prefrontal pyramidal neuron. Long-term synaptic plasticity in the model is governed by a calcium- and dopamine-dependent learning rule, in which dopamine exerts its action via D1 and D2 dopamine receptors in a concentration-dependent manner. Our results support a novel function of dopamine in the prefrontal cortex, namely that it controls the synaptic modification threshold between long-term depression and potentiation in pyramidal neurons. The proposed theoretical framework explains a wide range of experimental results and provides a link between in vitro and in vivo studies of dopaminergic plasticity modulation. It also suggests that dopamine may constitute a new player in metaplastic and homeostatic processes in the prefrontal cortex.
前额叶皮层中的长期记忆是适应性执行控制的必要组成部分，并且强烈受到多巴胺的调制。然而，这种多巴胺调制的功能意义仍然难以捉摸。关于多巴胺依赖性塑造前额叶长期可塑性的体外实验结果往往不一致，总的来说，描绘出一幅复杂的画面。由于两种实验条件之间存在很强的差异，通常也很难将这些发现与体内观察结果联系起来。本研究通过将其置于皮层可塑性的 Bienenstock-Cooper-Munro 理论框架内，提出了一种统一的观点，即多巴胺在前额叶皮层中的功能作用。我们通过一个前额叶锥体神经元的多腔 Hodgkin-Huxley 模型来研究长期可塑性的多巴胺调制。该模型中的长期突触可塑性由一个钙依赖性和多巴胺依赖性的学习规则控制，其中多巴胺通过 D1 和 D2 多巴胺受体以浓度依赖的方式发挥作用。我们的研究结果支持多巴胺在前额叶皮层中的一种新功能，即它控制着锥体神经元中长时程压抑和增强之间的突触修饰阈值。所提出的理论框架解释了广泛的实验结果，并为多巴胺可塑性调制的体外和体内研究之间建立了联系。它还表明，多巴胺可能是前额叶皮层中超塑性和同型性过程的新参与者。
