An Extracellular Perspective on CNS Maturation: Perineuronal Nets and the Control of Plasticity

Abstract

During restricted time windows of postnatal life, called critical periods, neural circuits are highly plastic and are shaped by environmental stimuli. In several mammalian brain areas, from the cerebral cortex to the hippocampus and amygdala, the closure of the critical period is dependent on the formation of perineuronal nets. Perineuronal nets are a condensed form of an extracellular matrix, which surrounds the soma and proximal dendrites of subsets of neurons, enwrapping synaptic terminals. Experimentally disrupting perineuronal nets in adult animals induces the reactivation of critical period plasticity, pointing to a role of the perineuronal net as a molecular brake on plasticity as the critical period closes. Interestingly, in the adult brain, the expression of perineuronal nets is remarkably dynamic, changing its plasticity-associated conditions, including memory processes. In this review, we aimed to address how perineuronal nets contribute to the maturation of brain circuits and the regulation of adult brain plasticity and memory processes in physiological and pathological conditions.

Impact of Perineuronal Nets on Electrophysiology of Parvalbumin Interneurons, Principal Neurons, and Brain Oscillations: A Review

“…Two studies have shown circadian/diurnal changes, with higher numbers or intensity of PNNs in the dark phase in rodents (Pantazopoulos et al, 2020 ; Harkness et al, 2021 ). Given that PNNs are altered in many ways throughout central nervous system development, and their maturation is brain region-specific and generally coincides with the end of critical periods of plasticity (for a recent review see Carulli and Verhaagen, 2021 ), it is not surprising that numerous studies have also demonstrated changes in PNNs or their composition during aging (Tanaka and Mizoguchi, 2009 ; Karetko-Sysa et al, 2014 ; Brewton et al, 2016 ; Foscarin et al, 2017 ; Richard et al, 2018 ; Ueno et al, 2019 ; Mafi et al, 2020 ). Overall, changes in PNNs and PV neurons after physiological stimuli appear to be specific to the physiological stimulus, brain region, and the circuits in which PNN-surrounded neurons are embedded.…”

New insights into glial scar formation after spinal cord injury

“…Rampant protease secretion from immune cells propagates their entry through the blood-brain barrier after traumatic injury (Noble et al 2002) or neurodegenerative disorders (Crapser et al 2020) contributing to secondary damage and loss of synapses. However, the fine control of local protease release from growth cones or the leading processes of migrating cells is critically important during developmental pathfinding (Brooks et al 2013) as well as during regeneration or sprouting in the adult (Krystosek and Seeds 1984;Luo et al 2018;Tran et al 2018a;Carulli and Verhaagen 2021;Tran and Silver 2021).…”

Neural Tissue Homeostasis and Repair Is Regulated via CS and DS Proteoglycan Motifs

“…Progenitor cells over-expressing NG2 PG also improve re-myelination through EGFR mediated cell signaling ( Keirstead and Blakemore, 1999 ; Aguirre et al, 2007 ). PNNs surrounding the soma and dendrites of a number of neuronal cell types are prevalent during neural development and maturation ( Carulli and Verhaagen, 2021 ). A similar structure, the perinodal ECM surrounds the axonal nodes of Ranvier and appear after re-myelination, acting as a protective ion-diffusion barrier ( Bekku and Oohashi, 2019 ; Fawcett et al, 2019 ).…”

“…With the identification of the multiple molecular determinants that provide neuronal connectivity, and with new insights into the modulatory extracellular information regulating axon guidance, neural network and synapse formation, a better understanding of the complexity that neurons face in a living organism is beginning to emerge. Attention is now returning to an ancient regulator of cell-cell interaction: the ECM ( Dityatev and Schachner, 2006 ; Dityatev et al, 2010 ; Miyata and Kitagawa, 2017 ; Nicholson and Hrabětová, 2017 ; Ferrer-Ferrer and Dityatev, 2018 ; Quraishe et al, 2018 ; Cope and Gould, 2019 ; Long and Huttner, 2019 ; Chelyshev et al, 2020 ; Jain et al, 2020 ; Wilson et al, 2020 ; Carulli and Verhaagen, 2021 ; Kamimura and Maeda, 2021 ; Shabani et al, 2021 ; Su et al, 2021 ). Among the many matrix components that influence neuronal connectivity, recent studies on the CS-PGs and HS-PGs indicate these ancient molecules form dynamic scaffolds that not only provide a protective environment around cells but are also a source of directive cues that modulate neuronal behavior and synaptic plasticity in tissue development ( Haylock-Jacobs et al, 2011 ; Hayes and Melrose, 2018 ; Hayes et al, 2018 ; Karamanos et al, 2018 ; Hayes and Melrose, 2020a ; Shabani et al, 2021 ).…”