Intermittent Failure of Spike Propagation in Primary Afferent Neurons during Tactile Stimulation
Notice bibliographique
Résumé
Primary afferent neurons convey somatosensory information to the CNS. Low-threshold mechanoreceptors are classified as slow-adapting (SA) or rapid-adapting (RA) based on whether or not they spike repetitively during sustained tactile stimulation; the former are subclassified as Type 1 or 2 based on the regularity of their spiking. Recording in vivo from DRGs of mice, we observed irregular- and regular-spiking units consistent with SA1 and SA2 low-threshold mechanoreceptors, but some units, which we labeled “semiregular,” did not fit cleanly into the existing classification scheme. Analysis of their spiking revealed integer-multiple patterning in which spike trains comprised a fundamental interspike interval and multiples thereof. Integer-multiple-patterned spiking was reproduced by randomly removing spikes from an otherwise regular spike train, suggesting that semiregular units represent SA2 units in which some spikes are “missing.” We hypothesized that missing spikes arose from intermittent failure of spikes to initiate or to propagate. Intermittent failure of spike initiation was ruled out by several observations: integer-multiple-patterned spiking was not induced by intradermal lidocaine, was independent of stimulus modality (mechanical vs optogenetic), and could not be reproduced in a conductance-based model neuron given constant input. On the other hand, integer-multiple-patterned spiking was induced by application of lidocaine to the DRG, thus pinpointing intermittent failure of spike propagation as the basis for integer-multiple-patterned spiking. Indeed, half of all SA2 units exhibited some missing spikes, mostly at low rate (<5%), which suggests that axons are efficient in using the lowest safety factor capable of producing near-perfect propagation reliability. SIGNIFICANCE STATEMENT The impedance mismatch at axon branch points can impede spike propagation. Reliability of spike propagation across branch points remains an open question and is especially important for primary afferents whose spikes must cross a T-junction to reach the CNS. Past research on propagation reliability has relied almost entirely on simulations and in vitro experiments. Here, recording in vivo , we linked a distinctive pattern of spiking to the intermittent failure of spike propagation at the T-junction. The rarity of failures argues that safety factor is high under physiological conditions, yet the occurrence of such failures argues that safety factor is just high enough to ensure near-perfect reliability, consistent with a good balance between propagation reliability and energy efficiency.
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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