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Aberrant perineuronal nets alter spinal circuits, impair motor function, and increase plasticity

2022· article· en· W4294549782 on OpenAlexaff
Judith Sánchez-Ventura, Carla Canal, José Manuel Hidalgo, Clara Penas, Xavier Navarro, Abel Torres‐Espín, Karim Fouad, Esther Udina

Bibliographic record

VenueExperimental Neurology · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProteoglycans and glycosaminoglycans research
Canadian institutionsWomen and Children’s Health Research InstituteUniversity of Alberta
FundersEuropean Social FundEuropean Regional Development FundCentro de Investigación Biomédica en Red sobre Enfermedades NeurodegenerativasUniversitat Autònoma de BarcelonaAgència de Gestió d'Ajuts Universitaris i de RecercaFundació la Marató de TV3Ministerio de Economía y CompetitividadGeneralitat de CatalunyaEuropean CommissionMinisterio de Ciencia, Innovación y Universidades
KeywordsPerineuronal netNeuroscienceSpinal cordExcitatory postsynaptic potentialSpinal cord injuryCorticospinal tractMotor cortexBiologyMotor neuronElectrophysiologyNeuroplasticityInterneuronInhibitory postsynaptic potentialMedicineStimulation

Abstract

fetched live from OpenAlex

Perineuronal nets (PNNs) are a specialized extracellular matrix that have been extensively studied in the brain. Cortical PNNs are implicated in synaptic stabilization, plasticity inhibition, neuroprotection, and ionic buffering. However, the role of spinal PNNs, mainly found around motoneurons, is still unclear. Thus, the goal of this study is to elucidate the role of spinal PNNs on motor function and plasticity in both intact and spinal cord injured mice. We used transgenic mice lacking the cartilage link protein 1 (Crtl1 KO mice), which is implicated in PNN assembly. Crtl1 KO mice showed disorganized PNNs with an altered proportion of their components in both motor cortex and spinal cord. Behavioral and electrophysiological tests revealed motor impairments and hyperexcitability of spinal reflexes in Crtl1 KO compared to WT mice. These functional outcomes were accompanied by an increase in excitatory synapses around spinal motoneurons. Moreover, following spinal lesions of the corticospinal tract, Crtl1 KO mice showed increased contralateral sprouting compared to WT mice. Altogether, the lack of Crtl1 generates aberrant PNNs that alter excitatory synapses and change the physiological properties of motoneurons, overall altering spinal circuits and producing motor impairment. This disorganization generates a permissive scenario for contralateral axons to sprout after injury.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.551
Threshold uncertainty score0.860

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.012
GPT teacher head0.261
Teacher spread0.249 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations11
Published2022
Admission routes1
Has abstractyes

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