A Molecular Framework That Links Dynamic Perineuronal Net Remodelling to Learning-Related Plasticity of Parvalbumin-Positive Interneurons

Abstract

Our fundamental capability to learn and memorize is endowed by the vivid, experience-driven adaptability of the neuronal connections within our central nervous system, termed as neuronal plasticity. An extensive body of research indicates that parvalbumin-positive interneurons (PVI) are profoundly involved in this process, but the molecular mechanisms underlying PVI plasticity are still inferiorly understood. Perineuronal nets (PNNs) are specialized extracellular matrices that principally sheath PVIs, and have been coined as foremost candidates in regulating activity-dependent PVI plasticity. Despite their robust structure, PNNs dynamically wax and wane in an experience-dependent manner, and recent lines of evidence imply that this process dictates PVI plasticity and is critical for learning and memory consolidation in the adult brain. However, an overarching comprehension of the precise modulation and mechanism of action of PNNs in this context remains elusive. To address this knowledge gap, recent studies regarding the molecular mechanisms that dynamically control PNN stability will be brought into focus and their role in regulating neuronal plasticity will be evaluated. In the current work, it is ascertained that several PNN-effector proteins, including metalloproteinases and sulphotransferases, exhibit a dynamic expression pattern throughout different stages of memory consolidation and are required to act in parallel to orchestrate learning-related adaptations in PVI plasticity. Based on these interpretations, a molecular framework is proposed that substantiates a working model in which dynamic remodelling of PNNs accounts for the rapid finetuning of PVI excitability in order to facilitate the formation of new memories.