Department of Dynamics and Control, Beihang University, No. 37 Xueyuan Road, HaiDian District, Beijing 100191, China.
College of Information Science and Technology, Donghua University, No. 2999 Renmin North Road, Songjiang District, Shanghai 201620, China.
Cereb Cortex. 2024 Jun 4;34(6). doi: 10.1093/cercor/bhae258.
Serotonin (5-HT) regulates working memory within the prefrontal cortex network, which is crucial for understanding obsessive-compulsive disorder. However, the mechanisms how network dynamics and serotonin interact in obsessive-compulsive disorder remain elusive. Here, we incorporate 5-HT receptors (5-HT1A, 5-HT2A) and dopamine receptors into a multistable prefrontal cortex network model, replicating the experimentally observed inverted U-curve phenomenon. We show how the two 5-HT receptors antagonize neuronal activity and modulate network multistability. Reduced binding of 5-HT1A receptors increases global firing, while reduced binding of 5-HT2A receptors deepens attractors. The obtained results suggest reward-dependent synaptic plasticity mechanisms may attenuate 5-HT related network impairments. Integrating serotonin-mediated dopamine release into circuit, we observe that decreased serotonin concentration triggers the network into a deep attractor state, expanding the domain of attraction of stable nodes with high firing rate, potentially causing aberrant reverse learning. This suggests a hypothesis wherein elevated dopamine concentrations in obsessive-compulsive disorder might result from primary deficits in serotonin levels. Findings of this work underscore the pivotal role of serotonergic dysregulation in modulating synaptic plasticity through dopamine pathways, potentially contributing to learned obsessions. Interestingly, serotonin reuptake inhibitors and antidopaminergic potentiators can counteract the over-stable state of high-firing stable points, providing new insights into obsessive-compulsive disorder treatment.
血清素（5-HT）调节前额叶皮层网络中的工作记忆，这对于理解强迫症至关重要。然而，网络动力学和血清素在强迫症中如何相互作用的机制仍不清楚。在这里，我们将 5-HT 受体（5-HT1A、5-HT2A）和多巴胺受体纳入一个多稳定前额叶皮层网络模型，复制了实验观察到的倒 U 型曲线现象。我们展示了这两种 5-HT 受体如何拮抗神经元活动并调节网络的多稳定性。减少 5-HT1A 受体的结合会增加全局放电，而减少 5-HT2A 受体的结合会加深吸引子。所得结果表明，奖励依赖的突触可塑性机制可能会减轻与 5-HT 相关的网络损伤。将血清素介导的多巴胺释放整合到回路中，我们观察到，血清素浓度的降低会使网络进入一个深吸引子状态，扩大具有高放电率的稳定节点的吸引域，可能导致异常的反向学习。这表明了一种假设，即在强迫症中多巴胺浓度的升高可能是由于血清素水平的主要缺陷所致。这项工作的发现强调了 5-羟色胺通过多巴胺途径调节突触可塑性的关键作用，这可能导致习得性强迫观念。有趣的是，血清素再摄取抑制剂和抗多巴胺增效剂可以对抗高放电稳定点的过度稳定状态，为强迫症的治疗提供了新的见解。
