Lateral lamina V projection neuron axon collaterals connect sensory processing across the dorsal horn of the mouse spinal cord DOI Creative Commons
Tyler J. Browne, Kelly M. Smith, Mark A. Gradwell

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 1, 2024

Spinal projection neurons (PNs) are defined by long axons that travel from their origin in the spinal cord to brain where they relay sensory information body. The existence and function of a substantial axon collateral network, also arising PNs remaining within cord, is less well appreciated. Here we use retrograde viral transduction strategy characterise novel subpopulation deep dorsal horn spinoparabrachial neurons. Brainbow assisted analysis confirmed virally labelled PN cell bodies formed discrete column lateral part Lamina V (LV

Language: Английский

Differential modification of ascending spinal outputs in acute and chronic pain states DOI Creative Commons
David A. Yarmolinsky,

Xiangsunze Zeng,

Natalie MacKinnon-Booth

et al.

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Pain hypersensitivity arises from the induction of plasticity in peripheral and spinal somatosensory neurons, which modifies nociceptive input to brain, altering pain perception. We applied longitudinal calcium imaging dorsal projection neurons determine whether how representation stimuli anterolateral tract, principal pathway transmitting signals changes between distinct states. In healthy mice, we identified stable outputs selective for cooling or warming a neuronal ensemble activated by noxious thermal mechanical stimuli. Induction acute sensitization topical capsaicin transiently re-tuned output encode low-intensity contrast, nerve injury resulted persistent suppression innocuous coupled with activation normally silent population high-threshold neurons. These results demonstrate differential modulation brain during neuropathic

Language: Английский

Citations

2
Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons DOI Creative Commons
Andrew M. Bell, Charlotte Utting, Allen C. Dickie

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(23)

Published: May 28, 2024

The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies perception of pain, itch, skin temperature. Despite its importance, our understanding this has been hampered by considerable functional molecular diversity constituent cells. Here, we use fluorescence-activated cell sorting isolate ALS neurons belonging Phox2a-lineage for single-nucleus RNA sequencing. We reveal five distinct clusters (ALS1-5) document their laminar distribution in using situ hybridization. identify three located predominantly laminae I–III dorsal horn (ALS1-3) two with bodies deeper (ALS4 ALS5). Our findings transcriptional logic neuronal adult mouse uncover identity previously identified classes projection neurons. also show these signatures can be used target groups retrograde viral tracing. Overall, provide valuable resource studying somatosensory biology targeting subclasses

Language: Английский

Citations

7
VLK drives extracellular phosphorylation of EphB2 to govern the EphB2-NMDAR interaction and injury-induced pain DOI Creative Commons
Kolluru D. Srikanth, Hajira Elahi, Praveen Chander

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 18, 2024

Abstract Phosphorylation of hundreds protein extracellular domains is mediated by two kinase families, yet the significance these kinases underexplored. Here, we find that presynaptic release tyrosine directed-ectokinase, Vertebrate Lonesome Kinase (VLK/Pkdcc), necessary and sufficient for direct interaction between EphB2 GluN1 at synapses, phosphorylation ectodomain EphB2, injury-induced pain. Pkdcc an essential gene in nervous system, VLK found synaptic vesicles, released from neurons a SNARE-dependent fashion. expressed nociceptive sensory where neuron-specific knockout renders mice impervious to post-surgical pain, without changing proprioception. defines mechanism regulates protein-protein non-opioid-dependent pain response injury. One-Sentence Summary Synaptic interactions are regulated spinal cord.

Language: Английский

Citations

3
A Viral Labelling Study of Spinal Trigeminal Nucleus Caudalis Projection Neurons Targeting the Parabrachial Nucleus DOI Creative Commons
Saša Marić, Mehedi Hasan,

Madison L. Pounder

et al.

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(3)

Published: March 1, 2025

Projection neurons (PNs) in the Spinal Trigeminal Nucleus Caudalis (Sp5C) relay orofacial nociceptive information to higher brain regions such as thalamus and parabrachial nucleus (PBN). Our understanding of Sp5C PN organisation function has advanced less than parallel spinal cord output system despite their corresponding roles for transmission signals from region body respectively. Viral vectors are an established approach studying circuit connectivity nervous system, but different serotypes known produce variable results across circuits. As such, we sought validate utility two common viral research: retrograde adeno-associated virus serotype 2 (rgAAV) 9 (AAV9), identifying analysing PNs that project PBN. Following unilateral injections either into PBN, many projection were retrogradely labelled. For both serotypes, these labelled bilaterally with a strong bias ipsilateral Sp5C. Within Sp5C, similar levels labelling present superficial deep regions, contrasting previous work showed greater by AAV9 versus rgAAV. Comparisons age dependence when made young adult animals. Finally, demonstrate successful Cre-dependent recombination selectively express channelrhodopsin-2 neurons. Together, experiments show rgAAV transduction provide basis future study afferent efferent functions population health disease.

Language: Английский

Citations

0
Anatomical characterisation of somatostatin-expressing neurons belonging to the anterolateral system DOI Creative Commons
Wenhui Ma,

Erika Polgár,

Allen C. Dickie

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 20, 2025

Abstract Anterolateral system (ALS) spinal projection neurons are essential for pain perception. However, these cells heterogeneous, and there has been extensive debate about the roles of ALS populations in different dimensions. We recently performed single-nucleus RNA sequencing on a developmentally-defined subset neurons, identified 5 transcriptomic populations. One these, ALS4, consists that express Sst , gene coding somatostatin, we reported were located lateral part lamina V. Here use Cre mouse line to characterise define their axonal projections. find axons ascend mainly ipsilateral side, giving off collaterals throughout course cord. They target various brainstem nuclei, including parabrachial internal nucleus, posterior triangular medial dorsal thalamic nuclei. also show L4 segment is expressed by ~ 75% V around 120 -positive each side. Our findings indicate this relatively large population, based targets conclude they likely contribute affective-motivational dimension pain.

Language: Английский

Citations

0
An electrophysiologist’s guide to dorsal horn excitability and pain DOI Creative Commons
Ivan Rivera‐Arconada, Mark L. Baccei, J.A. López‐García

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: April 2, 2025

The dorsal horn of the spinal cord represents first site in central nervous system (CNS) where nociceptive signals are integrated. As a result, there has been rapid growth number studies investigating ionic mechanisms regulating excitability neurons under normal and pathological conditions. We believe that it is time to look back critically examine what picture emerges from this wealth studies. What actual types described literature based on electrophysiological criteria? Are these electrophysiologically-defined subpopulations strongly linked specific morphological, functional, or molecular traits? properties stable, can they change during development response peripheral injury? Here we provide an in-depth overview both early recent publications explore factors influencing neuronal (including intrinsic membrane synaptic transmission), how vary across distinct subtypes neurons, such altered by nerve tissue damage. meta-research presented below leads conclusion comprised highly heterogeneous which observed given neuron often fail easily predict other as biochemical phenotype morphology. This highlights need for future more fully interrogate multi-modal manner.

Language: Английский

Citations

0
Lateral lamina V projection neuron axon collaterals connect sensory processing across the dorsal horn of the mouse spinal cord DOI Creative Commons
Tyler J. Browne, Kelly M. Smith, Mark A. Gradwell

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 1, 2024

Spinal projection neurons (PNs) are defined by long axons that travel from their origin in the spinal cord to brain where they relay sensory information body. The existence and function of a substantial axon collateral network, also arising PNs remaining within cord, is less well appreciated. Here we use retrograde viral transduction strategy characterise novel subpopulation deep dorsal horn spinoparabrachial neurons. Brainbow assisted analysis confirmed virally labelled PN cell bodies formed discrete column lateral part Lamina V (LV

Language: Английский

Citations

2