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Record W4414428798 · doi:10.1101/2025.09.22.677841

Spinal dI3 neurons are involved in sustained motor adaptation elicited by low-threshold cutaneous afferents

2025· preprint· en· W4414428798 on OpenAlexafffund
E. STANLEY I. KHAN, Shahriar Nasiri, Sarah Chiasson, Lauren Couvrette, Alex M. Laliberté, Tuan V. Bui

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldNeuroscience
TopicNeuroscience and Neural Engineering
Canadian institutionsUniversity of Ottawa
FundersCanadian Institutes of Health Research
KeywordsStimulationInhibitory postsynaptic potentialSpinal cordExcitatory postsynaptic potentialInterneuronHindlimbAdaptation (eye)Motor system

Abstract

fetched live from OpenAlex

ABSTRACT Adaptation of muscle activity to meet a certain target or intention is traditionally attributed to supraspinal structures. However, evidence is mounting that this process can occur within the spinal cord through intrinsic plasticity and circuit reorganization. Here, we investigate the role of a class of excitatory spinal interneurons, called dorsal interneuron 3 (dI3), in the acquisition of novel motor behaviors independent of supraspinal input. Using a real-time closed-loop stimulation paradigm in spinalized mice, we promoted a persistent adaptation in the hindlimb position to be higher than its resting level by delivering saphenous nerve stimulation contingent on toe elevation. The stimulation intensities were calibrated to selectively recruit low-threshold mechanoreceptors (LTMRs). To test the contribution of dI3s in this motor adaptation, inhibitory DREADD (hM4Di) receptors were expressed in Isl1⁺/Vglut2⁺ cells, achieving reversible, cell-type-specific silencing of dI3s. Our results demonstrate that stimulation of cutaneous inputs to the spinal cord contingent on a certain positional goal can generate sustained changes in motor activity, in this case, in the form of elevation of toe position above a preset vertical threshold. Chemogenetic silencing of dI3s abolished this motor adaptation induced by activation of LTMRs. These findings indicate that dI3 activity is essential for a particular type of motor adaptation driven primarily by LTMR input. NEW & NOTEWORTHY We developed a real-time, closed-loop stimulation paradigm in spinalized mice using kinematic video tracking to trigger electrical stimulation of the saphenous nerve. We discovered that low-threshold stimulations targeting non-nociceptive cutaneous afferents can elicit sustained motor adaptations independently from supraspinal input. Furthermore, using two chemogenetic techniques to transiently inhibit a population of spinal neurons, called dI3s, we found that these neurons are crucial for integrating these low-threshold stimuli to elicit sustained changes in motor behaviour.

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)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
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 score0.060
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.002
Insufficient payload (model declined to judge)0.0000.000

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 head0.023
GPT teacher head0.237
Teacher spread0.214 · 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.

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

Citations0
Published2025
Admission routes2
Has abstractyes

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