Differential encoding of mammalian proprioception by voltage-gated sodium channels

Science Advances, Год журнала: 2025, Номер 11(2)

Опубликована: Янв. 8, 2025

Animals requiring purposeful movement for survival are endowed with mechanoreceptors, called proprioceptors, that provide essential sensory feedback from muscles and joints to spinal cord circuits, which modulates motor output. Despite the nature of proprioceptive signaling in daily life, mechanisms governing proprioceptor activity poorly understood. Here, we identified nonredundant roles two voltage-gated sodium channels (Na V s), Na 1.1 1.6, mammalian proprioception. Deletion 1.6 somatosensory neurons cKO mice) causes severe deficits accompanied by loss transmission, contrasts our previous findings using similar mouse models target ). In animals, observed impairments end-organ structure a marked reduction skeletal muscle myofiber size were absent mice. We attribute differential contributions distinct cellular localization patterns. Collectively, evidence s uniquely shape neural within modality.

Язык: Английский

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Modulation of Sensory Input to the Spinal Cord by Peripheral Afferent Fibres via GABAergic Astrocytes

European Journal of Neuroscience, Год журнала: 2025, Номер 61(6)

Опубликована: Март 1, 2025

ABSTRACT A long‐lasting GABA‐dependent increase in the excitability of afferent fibres, and thus modulation sensory input to spinal cord, may be evoked by epidural polarization. However, direct effects fibre polarization are short‐lasting sustained their appears secondary release GABA from nearby astrocytes. We have now investigated whether stimulation a peripheral nerve, previously attributed synaptically intraspinal field potentials, is similar way. as neither its dependence on nor relays been investigated, we addressed question epidurally stimulated fibres following nerve does or not depend it might mediated The conditioning tibial were evaluated changes both Group I II muscle afferents, estimated action potentials recorded nerves dorsal horn respectively acute experiments deeply anaesthetized rats. afferents was increased and/or cutaneous but afferents. significantly weakened blocking channels gabazine astrocyte toxin L‐alpha‐aminoadipic acid (L‐AAA), indicating that modulated GABAergic astrocytes, new role played

Язык: Английский

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Ontogeny of the spinal cord dorsal horn

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 15, 2025

Summary The dorsal horn of the mammalian spinal cord is an exquisite example form serving function. It comprised diverse neuronal populations stacked into laminae, each which receives different circuit connections and plays specialized roles in behavior. An outstanding question how this organization emerges during development from apparently homogeneous pool neural progenitors. Here, we found that neurons are diversified by time, with families related cell types born as temporal cohorts, a spatial-molecular gradient specifies full array individual types. Excitatory then settle chronotopic arrangement transforms their progressive birthdates anatomical order. This establishes these also required for spatial inhibitory sensory axons. work reveals essential ontogenetic principles shape progenitors architecture subserve sensorimotor Highlights - Temporal cohorts late-born give rise to Sequentially-born excitatory neuron adjacent laminae Laminar structure specifically requires (but not or sensory) Graded expression Zic transcription factors directs fine identity

Язык: Английский

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Functional synaptic connectivity of engrafted spinal cord neurons with locomotor circuitry in the injured spinal cord

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 5, 2025

Spinal cord injury (SCI) results in significant neurological deficits, with no currently available curative therapies. Neural progenitor cell (NPC) transplantation has emerged as a promising approach for neural repair, graft-derived neurons (GDNs) can integrate into the host spinal and support axon regeneration. However, mechanisms underlying functional recovery remain poorly understood. In this study, we investigate synaptic integration of NPC-derived locomotor circuits, projection patterns distinct neuronal subtypes, their potential to modulate motor circuit activity. Using transsynaptic tracing mouse thoracic contusion SCI model, found that form connections albeit at low frequencies. Furthermore, mapped projections V0C V2a interneurons, revealing termination within laminae. To assess integration, employed chemogenetic activation GDNs, which induced muscle activity subset transplanted animals. NPC alone did not significantly improve recovery, highlighting key challenge field. Our findings suggest while GDNs circuits activity, connectivity remains limiting factor recovery. Future studies should focus on enhancing graft-host optimizing strategies maximize therapeutic benefits SCI.

Язык: Английский

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Spatial, transcriptomic, and epigenomic analyses link dorsal horn neurons to chronic pain genetic predisposition

Cell Reports, Год журнала: 2024, Номер 43(11), С. 114876 - 114876

Опубликована: Окт. 24, 2024

Язык: Английский

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Modulation of sensory input to the spinal cord: Contribution of focal epidural polarization and of GABA released by interneurons and glial cells

European Journal of Neuroscience, Год журнала: 2024, Номер 60(5), С. 5019 - 5039

Опубликована: Авг. 5, 2024

Modulation of input from primary afferent fibres has long been examined at the level first relays these fibres. However, recent studies reveal that to spinal cord may also be modulated very entry grey matter before action potentials in intraspinal collaterals reach their target neurons. Such modulation greatly depends on actions GABA via extrasynaptic membrane receptors. In reported study we hypothesized increase excitability following epidural polarization close site where leave dorsal columns is due release two sources: not only GABAergic interneurons but glial cells. We present evidence, primo, released both sources contributes a long-lasting and shortening refractory period epidurally stimulated and, secondo, effects are more critical for changes than direct DC The experiments were carried out deeply anaesthetized rats which compound evoked hindlimb peripheral nerves by column stimulation used as measure throws new light networks mechanisms underlying restoration functions.

Язык: Английский

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Modulation of input to the spinal cord; contribution of GABA released by interneurons and glial cells by polarization at the entry of sensory information

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 4, 2024

ABSTRACT Modulation of input from primary afferent fibres has long been examined at the level first relay neurons these fibres. However, recent studies reveal that to spinal cord may also be modulated before action potentials in intraspinal collaterals reach their target neurons, even very entry grey matter. Such modulation greatly depends on actions GABA via extrasynaptic membrane receptors. In reported study we hypothesized increase excitability following epidural polarization close site where leave dorsal columns is due release two sources: not only terminals GABAergic interneurons but glial cells. We present evidence, primo, both sources contributes a long-lasting and shortening refractory period epidurally stimulated afferents and, secondo, effects GABA-containing cells are more critical for changes than direct The experiments were carried out deeply anaesthetized rats which compound evoked hindlimb peripheral nerves by column stimulation used as measure throws new light networks mechanisms underlying restoration functions.

Язык: Английский

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Calcium homeostasis restoration in pyramidal neurons through micrometer-scale wireless electrical stimulation in spinal cord injured mice

Biochemical and Biophysical Research Communications, Год журнала: 2024, Номер 735, С. 150487 - 150487

Опубликована: Июль 31, 2024

Язык: Английский

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Differential encoding of mammalian proprioception by voltage-gated sodium channels

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 28, 2024

Abstract Animals that require purposeful movement for survival are endowed with mechanosensory neurons called proprioceptors provide essential sensory feedback from muscles and joints to spinal cord circuits, which modulates motor output. Despite the nature of proprioceptive signaling in daily life, mechanisms governing proprioceptor activity poorly understood. Here, we have identified distinct nonredundant roles two voltage-gated sodium channels (NaVs), NaV1.1 NaV1.6, mammalian proprioception. Deletion NaV1.6 somatosensory (NaV1.6 cKO mice) causes severe deficits accompanied by complete loss transmission, contrasts our previous findings using similar mouse models target (NaV1.1 ). In animals, caused non-cell- autonomous impairments end-organs skeletal muscle were absent mice. We attribute differential contribution function cellular localization patterns. Collectively, these data first evidence NaV subtypes uniquely shape neurotransmission within a modality. Teaser Voltage gated differentially encode proprioception via

Язык: Английский

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Inter‐Strain Differences in the Lumbar Spinal Cord Anatomy and Neuromorphology: Wistar Versus Dark Agouti Rats

The Journal of Comparative Neurology, Год журнала: 2024, Номер 532(10)

Опубликована: Окт. 1, 2024

ABSTRACT Rat strains differ in physiology, behavior, and recovery after central nervous system injury. To assess these differences, we compared the gross local anatomy neuromorphology of lumbar spinal cord Wistar Dark Agouti (DA) strains. The key findings include (i) distinct spatial relationships between vertebrae segments two strains; (ii) rats have larger volumes gray white matter; (iii) DA smaller total neuronal populations, thus indicating an expectation populations; (iv) this was confirmed for interneurons expressing calbindin 28 kDa. But contrary to expectations, (v) had more numerous populations parvalbumin a population α‐motoneurons. Consequently, displayed divergent ratios specific populations. Researchers should consider inter‐strain differences when comparing data across different

Язык: Английский

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