Do perineuronal nets stabilize the engram of a synaptic circuit?

Lev‐Ram, Varda; Lemieux, Sakina P.; Deerinck, Thomas J.; Bushong, Eric A.; Toyama, Brandon H.; Perez, Alex; Pritchard, Denise R.; Park, Sung Kyu R.; McClatchy, Daniel B.; Savas, Jeffrey N.; Taylor, Susan S.; Ellisman, Mark H.; Yates, John R.; Tsien, Roger Y.

doi:10.1101/2023.04.09.536164

Cited by 3 publications

(2 citation statements)

References 53 publications

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“…Neurocan deficiency reduces late-phase LTP stability [ 60 ], brevican ablation significantly impairs LTP [ 61 ], and depletion of its binding partner tenascin-R also reduces LTP [ 62 ]. Knockout of the related glycoprotein tenascin-C results in a complete failure in LTD induction and impaired LTP development, likely due to reduced L-type VDCC channel signaling [ 63 , 64 ].…”

Section: Pnns’ Structure and Functionsmentioning

confidence: 99%

Perineuronal Nets in the CNS: Architects of Memory and Potential Therapeutic Target in Neuropsychiatric Disorders

Li,

Wu,

et al. 2024

IJMS

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The extracellular matrix (ECM) within the brain possesses a distinctive composition and functionality, influencing a spectrum of physiological and pathological states. Among its constituents, perineuronal nets (PNNs) are unique ECM structures that wrap around the cell body of many neurons and extend along their dendrites within the central nervous system (CNS). PNNs are pivotal regulators of plasticity in CNS, both during development and adulthood stages. Characterized by their condensed glycosaminoglycan-rich structures and heterogeneous molecular composition, PNNs not only offer neuroprotection but also participate in signal transduction, orchestrating neuronal activity and plasticity. Interfering with the PNNs in adult animals induces the reactivation of critical period plasticity, permitting modifications in neuronal connections and promoting the recovery of neuroplasticity following spinal cord damage. Interestingly, in the adult brain, PNN expression is dynamic, potentially modulating plasticity-associated states. Given their multifaceted roles, PNNs have emerged as regulators in the domains of learning, memory, addiction behaviors, and other neuropsychiatric disorders. In this review, we aimed to address how PNNs contribute to the memory processes in physiological and pathological conditions.

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Section: Pnns’ Structure and Functionsmentioning

confidence: 99%

Perineuronal Nets in the CNS: Architects of Memory and Potential Therapeutic Target in Neuropsychiatric Disorders

Li,

Wu,

et al. 2024

IJMS

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“…Based on the long-lived nature of some ECM/PNN molecules 29,30 , we examined activity-dependent ECM/PNN changes in living tissues, hypothesizing that this stable and long-lived structures around neurons enables memories encoded in synapses to persist over time 28,29 . To better characterize these structures, we first examine cultured neurons using both antibodies to proteoglycans and a HA-binding protein, used previously to study hyaluronan synthesis during neuronal development 31 .…”

Section: Introductionmentioning

confidence: 99%

Perineuronal nets and the neuronal extracellular matrix can be imaged by genetically encoded labeling of HAPLN1in vitroandin vivo

Lemieux,

Lev-Ram,

Tsien

et al. 2023

Preprint

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Neuronal extracellular matrix (ECM) and a specific form of ECM called the perineuronal net (PNN) are important structures for central nervous system (CNS) integrity and synaptic plasticity. PNNs are distinctive, dense extracellular structures that surround parvalbumin (PV)-positive inhibitory interneurons with openings at mature synapses. Enzyme-mediated PNN disruption can erase established memories and re-open critical periods in animals, suggesting that PNNs are important for memory stabilization and conservation. Here, we characterized the structure and distribution of several ECM/PNN molecules around neurons in culture, brain slice, and whole mouse brain. While specific lectins are well-established as PNN markers and label a distinct, fenestrated structure around PV neurons, we show that other CNS neurons possess similar extracellular structures assembled around hyaluronic acid, suggesting a PNN-like structure of different composition that is more widespread. We additionally report that genetically encoded labeling of hyaluronan and proteoglycan link protein 1 (HAPLN1) reveals a PNN-like structure around many neuronsin vitroandin vivo. Our findings add to our understanding of neuronal extracellular structures and describe a new mouse model for monitoring live ECM dynamics.

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Perineuronal Net Microscopy: From Brain Pathology to Artificial Intelligence

Paveliev,

Egorchev,

Musin

et al. 2024

IJMS

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Perineuronal nets (PNN) are a special highly structured type of extracellular matrix encapsulating synapses on large populations of CNS neurons. PNN undergo structural changes in schizophrenia, epilepsy, Alzheimer’s disease, stroke, post-traumatic conditions, and some other brain disorders. The functional role of the PNN microstructure in brain pathologies has remained largely unstudied until recently. Here, we review recent research implicating PNN microstructural changes in schizophrenia and other disorders. We further concentrate on high-resolution studies of the PNN mesh units surrounding synaptic boutons to elucidate fine structural details behind the mutual functional regulation between the ECM and the synaptic terminal. We also review some updates regarding PNN as a potential pharmacological target. Artificial intelligence (AI)-based methods are now arriving as a new tool that may have the potential to grasp the brain’s complexity through a wide range of organization levels—from synaptic molecular events to large scale tissue rearrangements and the whole-brain connectome function. This scope matches exactly the complex role of PNN in brain physiology and pathology processes, and the first AI-assisted PNN microscopy studies have been reported. To that end, we report here on a machine learning-assisted tool for PNN mesh contour tracing.

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Do perineuronal nets stabilize the engram of a synaptic circuit?

Cited by 3 publications

References 53 publications

Perineuronal Nets in the CNS: Architects of Memory and Potential Therapeutic Target in Neuropsychiatric Disorders

Perineuronal Nets in the CNS: Architects of Memory and Potential Therapeutic Target in Neuropsychiatric Disorders

Perineuronal nets and the neuronal extracellular matrix can be imaged by genetically encoded labeling of HAPLN1in vitroandin vivo

Perineuronal Net Microscopy: From Brain Pathology to Artificial Intelligence

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