Perineuronal nets stabilize the grid cell network

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Jan. 11, 2021

Abstract Grid cells are part of a widespread network which supports navigation and spatial memory. Stable grid patterns appear late in development, concert with extracellular matrix aggregates termed perineuronal nets (PNNs) that condense around inhibitory neurons. It has been suggested PNNs stabilize synaptic connections long-term memories, but their role the cell remains elusive. We show removal leads to lower spiking activity, reduces cells’ ability create stable representations novel environment. Furthermore, animals disrupted PNNs, exposure arena corrupted spatiotemporal relationships within modules, stored familiar arena. Finally, we PNN entorhinal cortex distorted downstream hippocampal Together this work suggests provide key stabilizing element for network.

Language: Английский

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Development and Functional Diversification of Cortical Interneurons

Neuron, Journal Year: 2018, Volume and Issue: 100(2), P. 294 - 313

Published: Oct. 1, 2018

Language: Английский

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Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity

Cell, Journal Year: 2020, Volume and Issue: 182(2), P. 388 - 403.e15

Published: July 1, 2020

Language: Английский

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The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function

Nature reviews. Neuroscience, Journal Year: 2019, Volume and Issue: 20(8), P. 451 - 465

Published: July 1, 2019

Language: Английский

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Critical period regulation across multiple timescales

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(38), P. 23242 - 23251

Published: June 5, 2020

Brain plasticity is dynamically regulated across the life span, peaking during windows of early life. Typically assessed in physiological range milliseconds (real time), these trajectories are also influenced on longer timescales developmental time (nurture) and evolutionary (nature), which shape neural architectures that support plasticity. Properly sequenced critical periods circuit refinement build up complex cognitive functions, such as language, from more primary modalities. Here, we consider recent progress biological basis a unifying rubric for understanding multiple timescales. Notably, maturation parvalbumin-positive (PV) inhibitory neurons pivotal. These fast-spiking cells generate gamma oscillations associated with period plasticity, sensitive to circadian gene manipulation, emerge at different rates brain regions, acquire perineuronal nets age, may be by epigenetic factors over generations. features provide further novel insight into impact adversity neurodevelopmental risk mental disorders.

Language: Английский

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Environmental influences on the pace of brain development

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(6), P. 372 - 384

Published: April 28, 2021

Childhood socio-economic status (SES), a measure of the availability material and social resources, is one strongest predictors lifelong well-being. Here we review evidence that experiences associated with childhood SES affect not only outcome but also pace brain development. We argue higher protracted structural development prolonged trajectory functional network segregation, ultimately leading to more efficient cortical networks in adulthood. hypothesize greater exposure chronic stress accelerates maturation, whereas access novel positive decelerates maturation. discuss impact variation on plasticity learning. provide generative theoretical framework catalyse future basic science translational research environmental influences Evidence suggests can its rate. Tooley, Bassett Mackey this suggest valence frequency early interact influence

Language: Английский

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Neuron–glia interactions in the pathophysiology of epilepsy

Nature reviews. Neuroscience, Journal Year: 2019, Volume and Issue: 20(5), P. 282 - 297

Published: Feb. 21, 2019

Language: Английский

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GABA-receptive microglia selectively sculpt developing inhibitory circuits

Cell, Journal Year: 2021, Volume and Issue: 184(15), P. 4048 - 4063.e32

Published: July 1, 2021

Language: Английский

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Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits

Science, Journal Year: 2019, Volume and Issue: 363(6425), P. 413 - 417

Published: Jan. 25, 2019

Inhibitory synapse specificity As neurons build circuits in the developing brain, they select not only what other to connect but also where on that neuron will touch base. Working mice, Favuzzi et al. found gene expression programs define subsets of interneurons postsynaptic partner those prefer a synapse. One class prefers onto cell body pyramidal neurons, another dendrites, and yet axon initial segment. Science , this issue p. 413

Language: Английский

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Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain

EBioMedicine, Journal Year: 2020, Volume and Issue: 58, P. 102919 - 102919

Published: July 31, 2020

BackgroundMicroglia, the brain's principal immune cell, are increasingly implicated in Alzheimer's disease (AD), but molecular interfaces through which these cells contribute to amyloid beta (Aβ)-related neurodegeneration unclear. We recently identified microglial contributions homeostatic and disease-associated modulation of perineuronal nets (PNNs), extracellular matrix structures that enwrap stabilize neuronal synapses, whether PNNs altered AD remains controversial.MethodsExtensive histological analysis was performed on male female 5xFAD mice at 4, 8, 12, 18 months age assess plaque burden, microgliosis, PNNs. Findings were validated postmortem tissue. The role neuroinflammation PNN loss investigated via LPS treatment, ability prevent or rescue disease-related reductions assessed by treating 3xTg-AD model with colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 deplete microglia.FindingsUtilizing mouse human cortical tissue, we report extensively lost proportion burden. Activated microglia closely associate engulf damaged brain, inclusions material evident microglia, while aggrecan, a critical component, deposits within dense-core plaques. Disease-associated parvalbumin (PV)+ interneurons, frequently coated PNNs, preceded coverage integrity impairments, similar phenotypes elicited wild-type following activation LPS. Chronic pharmacological depletion prevents loss, results observed aged mice, this occurs despite persistence.InterpretationWe conclude phenotypically facilitate plaque-dependent brain.FundingThe NIH (NIA, NINDS) Association.

Language: Английский

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