An optogenetic model of hindlimb spasticity after complete T9-T10 spinal cord transection in male and female C57bl/6 mice

DOI:10.34945/F5H308

DATASET CITATION

Goltash S., Khodr R., Bui T. V., Laliberte A. M. (2025) An optogenetic model of hindlimb spasticity after complete T9-T10 spinal cord transection in male and female C57bl/6 mice. Open Data Commons for Spinal Cord Injury. ODC-SCI:1276 http://doi.org/10.34945/F5H308

ABSTRACT

STUDY PURPOSE: The purpose of this study was to test the efficacy of optogenetic stimulation of cutaneous VGLUT2+ sensory afferents in eliciting spasticity-associated behaviours after spinal cord injury. A tri-hybrid transgenic mouse line was produced (Isl1-Cre : Vglut2-IRES2-FLPo-D : Ai80(RCFL-CatCh)-D) to express the CatCh channelrhodopsin variant with VGLUT2+ sensory afferents. These mice were then subjected to a T9-T10 complete spinal cord transection to induce spasticity. The primary goal of this work was to validate this mouse model for the study of hindlimb spasticity after spinal cord injury, where light could be used to simply and reliably elicit spasticity-associated behaviours.

DATA COLLECTED: EMG data from the tibialis anterior and gastrocnemius muscles of awake and freely behaving mice was collected in the weeks following a complete T9-T10 transection (2 wpi, 3 wpi, 4 wpi, 5 wpi, and 10 wpi : wpi=weeks post injury). Blue light was directed onto each of the paws of the mice through a transparent floored chamber. Each session was comprised of 9 light pulses directed to each hindpaw, as well as 2 control pulses directed away from the mouse (20 total sweeps). Amplitudes and latencies of the EMG responses were averaged across trials. Anatomical data examining the expression of markers of various sensory afferent subtypes were also collected to confirm the identities of the optogenetically stimulated sensory afferents. RNAScope in situ hybridization (VGLUT1, VGLUT2) and immunohistochemistry (TRPV1, CGRP, IB4, TDTOMATO) techniques were performed for these markers and cell counts were performed.

CONCLUSIONS: The results of these recordings demonstrated significant increases in the amplitude of EMG responses to the light stimulus from 2 wpi to 10 wpi, suggesting increased excitability of cutaneous sensorimotor pathways. Interestingly, this effect was significantly greater in the female cohort than in the males. Incidences of prolonged involuntary muscle contraction in response to the stimulus (fictive spasms) were also detected through EMG and visual observation during the testing period, supporting the presence of spasticity. As such, the optogenetic mouse model developed for this study appears to elicit spasticity-associated behaviours in SCI mice reliably and may be valuable for studying SCI-related limb spasticity mechanisms and therapeutic interventions

KEYWORDS

Spinal Cord Injury; spasticity; optogenetics

PROVENANCE / ORIGINATING PUBLICATIONS

• Goltash S, Khodr R, Bui TV, Laliberte AM. An optogenetic mouse model of hindlimb spasticity after spinal cord injury. Exp Neurol. 2025 Jan 23:115157. doi: 10.1016/j.expneurol.2025.115157. Epub ahead of print. PMID: 39863244.. https://pubmed.ncbi.nlm.nih.gov/39863244.

Publication where the data is presented

RELEVANT LINKS

NOTES

DATASET INFO

Contact: Bui Tuan (tuan.bui@uottawa.ca), Laliberte Alex (alalibe3@gmail.com)

Lab: Tuan Bui Laboratory

ODC-SCI Accession:1276

Records in Dataset: 118

Fields per Record: 268

Last updated: 2025-02-11

Date published: 2025-02-11

Downloads: 4

Files: 2

LICENSE

Creative Commons Attribution License (CC-BY 4.0)

FUNDING AND ACKNOWLEDGEMENTS

Ontario Early Researcher Award - Ontario Ministry of Research, Innovation and Science ER16-12-214 (TVB), Craig H. Neilsen Foundation grant 651093 (TVB), Canadian Institute of Health Research Project Grant PJT 180556 (TVB)

CONTRIBUTORS

Goltash, Sara

University of Ottawa

Khodr, Riham

University of Ottawa

Bui, Tuan V.

University of Ottawa

Laliberte, Alex M. [ORCID:0000-0002-3503-4177]

University of Ottawa