Perineuronal Nets effects on incentive-salience and neuronal connectivity

Abstract

The current literature over-prioritizes studying dysfunctional neuronal structures caused by incentive-salience-induced network variations. The purpose of this study is to clarify the cellular processes which regulate the development of the aforementioned neuronal structures. This will be done by modeling the role of Perineuronal Nets (PNNs) in connecting sub-cortical regions to the frontal cortex. The connections between these regions, which are facilitated by salience, are tremendously important because of the myriad disorders correlated with their altered connectivity. Critical literature regarding PNN cellular energetics and neuromodular connectivity will be evaluated. Then, a computational model will focus on representing bio-energetic regulation and axonal arborization stabilization. The model will be created using NetPyNE and will position the PNN as a stabilizer of dopaminergic feedback loops, impacting which structures solidify or mutate. Morphological modeling and parameter approximation will be used to capture further nuances. The model will also account for bio-energetic regulation and axonal arborization stabilization, specifically in relation to PNN roles as a PFC-to-subcortical connection stabilizer and how this affects the cognitive processes linked to early pruning in stabilizing regions. If accurately modeled, we predict that the PNN in the model will improve accuracy in representing sub-region connections and, therefore, help better approximate altered dopamine feedback loops.