Systems Neurobiology Laboratory, Salk Institute for Biological Studies San Diego, CA, USA.
Department of Cognitive Sciences, University of California Irvine, CA, USA ; Department of Computer Sciences, University of California Irvine, CA, USA.
Front Comput Neurosci. 2015 Mar 11;9:31. doi: 10.3389/fncom.2015.00031. eCollection 2015.
The dopaminergic system has been shown to control the amount of noise in the prefrontal cortex (PFC) and likely plays an important role in working memory and the pathophysiology of schizophrenia. We developed a model that takes into account the known receptor distributions of D1 and D2 receptors, the changes these receptors have on neuron response properties, as well as identified circuitry involved in working memory. Our model suggests that D1 receptor under-stimulation in supragranular layers gates internal noise into the PFC leading to cognitive symptoms as has been proposed in attention disorders, while D2 over-stimulation gates noise into the PFC by over-activation of cortico-striatal projecting neurons in infragranular layers. We apply this model in the context of a memory-guided saccade paradigm and show deficits similar to those observed in schizophrenic patients. We also show set-shifting impairments similar to those observed in rodents with D1 and D2 receptor manipulations. We discuss how the introduction of noise through changes in D1 and D2 receptor activation may account for many of the symptoms of schizophrenia depending on where this dysfunction occurs in the PFC.
多巴胺能系统被证明可以控制前额叶皮层（PFC）的噪声量，并可能在工作记忆和精神分裂症的病理生理学中发挥重要作用。我们开发了一种模型，该模型考虑了 D1 和 D2 受体的已知受体分布、这些受体对神经元反应特性的变化，以及与工作记忆相关的已识别电路。我们的模型表明，超颗粒层中 D1 受体的刺激不足会将内部噪声传入 PFC，从而导致注意力障碍中提出的认知症状，而 D2 受体过度刺激会通过过度激活颗粒下层的皮质纹状体投射神经元将噪声传入 PFC。我们将该模型应用于记忆引导扫视范式，并显示出与精神分裂症患者观察到的相似的缺陷。我们还显示了类似于在 D1 和 D2 受体操作的啮齿动物中观察到的设置转移障碍。我们讨论了通过改变 D1 和 D2 受体激活引入噪声如何根据该功能障碍在 PFC 中的位置而导致精神分裂症的许多症状。
