Reneaux Melissa, Gupta Rahul
School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India.
School of Computer and Systems Sciences, Jawaharlal Nehru University, New Delhi, India.
PLoS One. 2015 Dec 4;10(12):e0144378. doi: 10.1371/journal.pone.0144378. eCollection 2015.
The role of prefronto-mesoprefrontal system in the dopaminergic modulation of working memory during delayed response tasks is well-known. Recently, a dynamical model of the closed-loop mesocortical circuit has been proposed which employs a deterministic framework to elucidate the system's behavior in a qualitative manner. Under natural conditions, noise emanating from various sources affects the circuit's functioning to a great extent. Accordingly in the present study, we reformulate the model into a stochastic framework and investigate its steady state properties in the presence of constant background noise during delay-period. From the steady state distribution, global potential landscape and signal-to-noise ratio are obtained which help in defining robustness of the circuit dynamics. This provides insight into the robustness of working memory during delay-period against its disruption due to background noise. The findings reveal that the global profile of circuit's robustness is predominantly governed by the level of D1 receptor activity and high D1 receptor stimulation favors the working memory-associated sustained-firing state over the spontaneous-activity state of the system. Moreover, the circuit's robustness is further fine-tuned by the levels of excitatory and inhibitory activities in a way such that the robustness of sustained-firing state exhibits an inverted-U shaped profile with respect to D1 receptor stimulation. It is predicted that the most robust working memory is formed possibly at a subtle ratio of the excitatory and inhibitory activities achieved at a critical level of D1 receptor stimulation. The study also paves a way to understand various cognitive deficits observed in old-age, acute stress and schizophrenia and suggests possible mechanistic routes to the working memory impairments based on the circuit's robustness profile.
前额叶-中前额叶系统在延迟反应任务期间对工作记忆的多巴胺能调节作用已广为人知。最近，有人提出了一种闭环中皮质回路的动力学模型，该模型采用确定性框架以定性方式阐明系统行为。在自然条件下，来自各种来源的噪声在很大程度上影响回路的功能。因此，在本研究中，我们将该模型重新构建为随机框架，并研究其在延迟期存在恒定背景噪声时的稳态特性。从稳态分布中，获得了全局势景观和信噪比，这有助于定义回路动力学的鲁棒性。这为深入了解延迟期工作记忆抵抗背景噪声干扰的鲁棒性提供了思路。研究结果表明，回路鲁棒性的全局概况主要由D1受体活性水平决定，高D1受体刺激有利于系统的工作记忆相关持续放电状态而非自发活动状态。此外，回路的鲁棒性通过兴奋性和抑制性活动水平进一步微调，使得持续放电状态的鲁棒性相对于D1受体刺激呈现倒U形曲线。据预测，最稳健的工作记忆可能形成于在D1受体刺激的临界水平上实现的兴奋性和抑制性活动的微妙比例。该研究还为理解在老年、急性应激和精神分裂症中观察到的各种认知缺陷铺平了道路，并基于回路的鲁棒性概况提出了导致工作记忆受损的可能机制途径。
