Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity

Abstract

Perineuronal nets (PNNs) are unique extracellular matrix structures that wrap around certain neurons in the CNS during development and control plasticity in the adult CNS. They appear to contribute to a wide range of diseases/disorders of the brain, are involved in recovery from spinal cord injury, and are altered during aging, learning and memory, and after exposure to drugs of abuse. Here the focus is on how a major component of PNNs, chondroitin sulfate proteoglycans, control plasticity, and on the role of PNNs in memory in normal aging, in a tauopathy model of Alzheimer's disease, and in drug addiction. Also discussed is how altered extracellular matrix/PNN formation during development may produce synaptic pathology associated with schizophrenia, bipolar disorder, major depression, and autism spectrum disorders. Understanding the molecular underpinnings of how PNNs are altered in normal physiology and disease will offer insights into new treatment approaches for these diseases.

Perineuronal nets labeled by monoclonal antibody VC1.1 ensheath interneurons expressing parvalbumin and calbindin in the rat amygdala

“…There is extensive evidence that PNNs regulate synaptic plasticity (for reviews see Dityatev and Schachner, 2003; Hensch, 2005; Galtrey and Fawcett, 2007; Wang and Fawcett 2012; Sorg et al, 2016). PNNs form postnatally in an activity-dependent manner, and have been shown to mark the end of “critical periods” in the development of several systems including the ocular dominance columns of the visual cortex and the barrels of the somatosensory cortex (Wang and Fawcett, 2012).…”

“…PNNs appear to stabilize these basic synaptic connections and tend to restrict further synaptic plasticity. It has been suggested that PNNs may restrict synaptic plasticity by: (1) forming a physical barrier between neurons and incoming axons; (2) providing a scaffold which binds molecules that inhibit the formation of new synapses; and/or (3) restricting the lateral mobility of AMPA receptors (Wang and Fawcett 2012; Sorg et al, 2016). …”

“…Recent studies have demonstrated that PNNs are formed during postnatal development and are critical for the regulation of a variety of synaptic functions including synaptic stabilization and synaptic plasticity (Galtrey and Fawcett, 2007; Berretta et al, 2015). The finding that PNNs and other components of the extracellular matrix are altered in several neurological and neuropsychiatric diseases suggests that a greater understanding of their structure and function could lead to novel therapies to treat these disorders (Viapiano and Matthews, 2006; Galtrey and Fawcett, 2007; Berretta et al, 2015; Maeda, 2015; Smith et al, 2015; Pantazopoulos and Berretta 2016; Sorg et al, 2016). …”

Description of a Novel Probiotic Concept: Implications for the Modulation of the Immune System

“…Thus, it has been demonstrated that chondroitin sulfate, as proteoglycan, is a major component of the peri-neuronal nets that control plasticity (Sorg et al, 2016).…”

Extracellular matrix and traumatic brain injury

“…During development, the localized expression of CSPGs influences axonal pathfinding (Carulli et al 2005; Wilson and Snow 2000). Once development is complete, CSPGs are mainly found in dense structures known as perineuronal nets, which serve to limit synaptic plasticity (Sorg et al 2016). …”