Stochastic Mesocortical Dynamics and Robustness of Working Memory during Delay-Period

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.