Formation of somatosensory detour circuits mediates functional recovery following dorsal column injury.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 07 2020
02 07 2020
Historique:
received:
15
01
2020
accepted:
15
06
2020
entrez:
4
7
2020
pubmed:
4
7
2020
medline:
2
12
2020
Statut:
epublish
Résumé
Anatomically incomplete spinal cord injuries can be followed by functional recovery mediated, in part, by the formation of intraspinal detour circuits. Here, we show that adult mice recover tactile and proprioceptive function following a unilateral dorsal column lesion. We therefore investigated the basis of this recovery and focused on the plasticity of the dorsal column-medial lemniscus pathway. We show that ascending dorsal root ganglion (DRG) axons branch in the spinal grey matter and substantially increase the number of these collaterals following injury. These sensory fibers exhibit synapsin-positive varicosities, indicating their integration into spinal networks. Using a monosynaptic circuit tracing with rabies viruses injected into the cuneate nucleus, we show the presence of spinal cord neurons that provide a detour pathway to the original target area of DRG axons. Notably the number of contacts between DRG collaterals and those spinal neurons increases by more than 300% after injury. We then characterized these interneurons and showed that the lesion triggers a remodeling of the connectivity pattern. Finally, using re-lesion experiments after initial remodeling of connections, we show that these detour circuits are responsible for the recovery of tactile and proprioceptive function. Taken together our study reveals that detour circuits represent a common blueprint for axonal rewiring after injury.
Identifiants
pubmed: 32616790
doi: 10.1038/s41598-020-67866-x
pii: 10.1038/s41598-020-67866-x
pmc: PMC7331809
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10953Références
Bareyre, F. M. et al. The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. Nat. Neurosci. 7, 269 (2004).
doi: 10.1038/nn1195
pmcid: 14966523
Kerschensteiner, M. et al. Remodeling of axonal connections contributes to recovery in an animal model of multiple sclerosis. J. Exp. Med. 200, 1027–1038 (2004).
doi: 10.1084/jem.20040452
pmcid: 15492125
Courtine, G. et al. Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Nat. Med. 14, 69–74 (2008).
doi: 10.1038/nm1682
pmcid: 18157143
Ueno, M., Hayano, Y., Nakagawa, H. & Yamashita, T. Intraspinal rewiring of the corticospinal tract requires target-derived brain-derived neurotrophic factor and compensates lost function after brain injury. Brain 135, 1253–1267 (2012).
doi: 10.1093/brain/aws053
pmcid: 22436236
Zörner, B. et al. Chasing central nervous system plasticity: the brainstem’s contribution to locomotor recovery in rats with spinal cord injury. Brain 137, 1716–1732 (2014).
doi: 10.1093/brain/awu078
pmcid: 24736305
Jacobi, A. et al. FGF22 signaling regulates synapse formation during post-injury remodeling of the spinal cord. EMBO J. 34, 1231–1243 (2015).
doi: 10.15252/embj.201490578
pmcid: 25766255
Hollis, E. R. II. et al. Remodelling of spared proprioceptive circuit involving a small number of neurons supports functional recovery. Nat. Commun. 6, 6079 (2015).
doi: 10.1038/ncomms7079
pmcid: 25597627
van den Brand, R. et al. Restoring voluntary control of locomotion after paralyzing spinal cord injury. Science 336, 1182–1185 (2012).
doi: 10.1126/science.1217416
Hilton, B. J. et al. Re-establishment of cortical motor output maps and spontaneous functional recovery via spared dorsolaterally projecting corticospinal neurons after dorsal column spinal cord injury in adult mice. J. Neurosci. 36, 4080–4092 (2016).
doi: 10.1523/JNEUROSCI.3386-15.2016
pmcid: 27053214
Henderson, L. A., Gustin, S. M., Macey, P. M., Wrigley, P. J. & Siddall, P. J. Functional reorganization of the brain in humans following spinal cord injury: evidence for underlying changes in cortical anatomy. J. Neurosci. 31(7), 2630–2711 (2011).
doi: 10.1523/JNEUROSCI.2717-10.2011
pmcid: 21325531
Jain, N., Catania, K. C. & Kaas, J. H. Deactivation and reactivation of somatosensory cortex after dorsal spinal cord injury. Nature 386(6624), 495–498 (1997).
doi: 10.1038/386495a0
pmcid: 9087408
Liao, C. C., Reed, J. L., Qi, H. X., Sawyer, E. K. & Kaas, J. H. Second-order spinal cord pathway contributes to cortical responses after long recoveries from dorsal column injury in squirrel monkeys. Proc. Natl. Acad. Sci. USA 115(16), 4258–4263 (2018).
doi: 10.1073/pnas.1718826115
pmcid: 29610299
Florence, S. L. & Kaas, J. H. Large-scale reorganization at multiple levels of the somatosensory pathway follows therapeutic amputation of the hand in monkeys. J. Neurosci. 15(12), 8083–8095 (1995).
doi: 10.1523/JNEUROSCI.15-12-08083.1995
pmcid: 8613744
Liao, C. C., DiCarlo, G. E., Gharbawie, O. A., Qi, H. X. & Kaas, J. H. Spinal cord neuron inputs to the cuneate nucleus that partially survive dorsal column lesions: a pathway that could contribute to recovery after spinal cord injury. J. Comp Neurol. 523(14), 2138–2160 (2015).
doi: 10.1002/cne.23783
pmcid: 25845707
Qi, H. X., Chen, L. M. & Kaas, J. H. Reorganization of somatosensory cortical areas 3b and 1 after unilateral section of dorsal columns of the spinal cord in squirrel monkeys. J. Neurosci. 31(38), 13662–13675 (2011).
doi: 10.1523/JNEUROSCI.2366-11.2011
pmcid: 21940457
Jain, N., Florence, S. L. & Kaas, J. H. Limits on plasticity in somatosensory cortex of adult rats: hindlimb cortex is not reactivated after dorsal column section. J. Neurophysiol. 73(4), 1537–1546 (1995).
doi: 10.1152/jn.1995.73.4.1537
pmcid: 7643165
Ghosh, A. et al. Rewiring of hindlimb corticospinal neurons after spinal cord injury. Nat. Neurosci. 13(1), 97–104 (2010).
doi: 10.1038/nn.2448
pmcid: 20010824
Endo, T., Spenger, C., Tominaga, T., Brené, S. & Olson, L. Cortical sensory map rearrangement after spinal cord injury: fMRI responses linked to Nogo signalling. Brain 130(Pt 11), 2951–2961 (2007).
doi: 10.1093/brain/awm237
pmcid: 17913768
Petitjean, H. et al. Dorsal horn parvalbumin neurons are gate-keepers of touch-evoked pain after nerve injury. Cell Rep. 13(6), 1246–1257 (2015).
doi: 10.1016/j.celrep.2015.09.080
pmcid: 26527000
Zeilhofer, H. U. et al. Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice. J. Comp. Neurol. 482(2), 123–141 (2005).
doi: 10.1002/cne.20349
pmcid: 15611994
Grimm, D., Kay, M. A. & Kleinschmidt, J. A. Helper virus-free, optically controllable, and two-plasmid-based production of adeno-associated virus vectors of serotypes 1 to 6. Mol. Ther. 7(6), 839–850 (2003).
doi: 10.1016/S1525-0016(03)00095-9
pmcid: 12788658
Klugmann, M. et al. AAV-mediated hippocampal expression of short and long Homer 1 proteins differentially affect cognition and seizure activity in adult rats. Mol. Cell. Neurosci. 28(2), 347–360 (2005).
doi: 10.1016/j.mcn.2004.10.002
pmcid: 15691715
Lang, C., Bradley, P. M., Jacobi, A., Kerschensteiner, M. & Bareyre, F. M. STAT3 promotes corticospinal remodelling and functional recovery after spinal cord injury. EMBO Rep. 14, 931–937 (2013).
doi: 10.1038/embor.2013.117
pmcid: 23928811
Bradley, P. M. et al. Corticospinal circuit remodeling after central nervous system injury is dependent on neuronal activity. J. Exp. Med. 216(11), 2503–2514 (2019).
doi: 10.1084/jem.20181406
pmcid: 31391209
De Ryck, M., Van Reempts, J., Duytschaever, H., Van Dueren, B. & Clincke, G. Neocortical localization of tactile/proprioceptive limb placing reactions in the rat. Brain Res. 573, 44–60 (1992).
doi: 10.1016/0006-8993(92)90112-M
pmcid: 1576535
Osakada, F. & Callaway, E. M. Design and generation of recombinant rabies virus vectors. Nat. Protocols 8(8), 1583–1601 (2013).
doi: 10.1038/nprot.2013.094
pmcid: 23887178
Wickersham, I. R., Finke, S., Conzelmann, K. K. & Callaway, E. M. Retrograde neuronal tracing with a deletion-mutant rabies virus. Nat. Methods 4, 47–49 (2007).
doi: 10.1038/nmeth999
Stepien, A. E., Tripodi, M. & Arber, S. Monosynaptic rabies virus reveals premotor network organization and synaptic specificity of cholinergic partition cells. Neuron 68, 456–472 (2010).
doi: 10.1016/j.neuron.2010.10.019
pmcid: 21040847
Ghanem, A. & Conzelmann, K. K. G gene-deficient single-round rabies viruses for neuronal circuit analysis. Virus Res. 216, 41–54 (2016).
doi: 10.1016/j.virusres.2015.05.023
pmcid: 26065596
Todd, A. J. Identifying functional populations among the interneurons in laminae I-III of the spinal dorsal horn. Mol. Pain 13, 1744806917693003 (2017).
doi: 10.1177/1744806917693003
pmcid: 28326935
Qin, C. et al. Modulation of neuronal activity in dorsal column nuclei by upper cervical spinal cord stimulation in rats. Neuroscience 164(2), 770–776 (2009).
doi: 10.1016/j.neuroscience.2009.08.001
pmcid: 19665525
Gradwell, M. A., Boyle, K. A., Callister, R. J., Hughes, D. I. & Graham, B. A. Heteromeric α/β glycine receptors regulate excitability in parvalbumin-expressing dorsal horn neurons through phasic and tonic glycinergic inhibition. J. Physiol. 595(23), 7185–7202 (2017).
doi: 10.1113/JP274926
pmcid: 28905384
Bareyre, F. M., Kerschensteiner, M., Misgeld, T. & Sanes, J. R. Transgenic labeling of the corticospinal tract for monitoring axonal responses to spinal cord injury. Nat. Med. 11(12), 1355–1360 (2005).
doi: 10.1038/nm1331
pmcid: 16286922
Shelton, S. B. et al. A simple, efficient tool for assessment of mice after unilateral cortex injury. J. Neurosci. Methods. 168(2), 431–442 (2008).
doi: 10.1016/j.jneumeth.2007.11.003
pmcid: 18164073
Darian-Smith, C. & Brown, S. Functional changes at periphery and cortex following dorsal root lesions in adult monkeys. Nat. Neurosci. 3(5), 476–481 (2000).
doi: 10.1038/74852
pmcid: 10769388
Lang, C., Guo, X., Kerschensteiner, M. & Bareyre, F. M. Single collateral reconstructions reveal distinct phases of corticospinal remodeling after spinal cord injury. PLoS ONE 7(1), e30461 (2012).
doi: 10.1371/journal.pone.0030461
pmcid: 22291960
Hubel, D. H., Wiesel, T. N. & LeVay, S. Plasticity of ocular dominance columns in monkey striate cortex. Philos Trans. R. Soc. Lond. B Biol. Sci. 278, 377–409 (1977).
doi: 10.1098/rstb.1977.0050
pmcid: 19791
Mariani, J. Elimination of synapses during the development of the central nervous system. Prog. Brain Res. 58, 383–392 (1983).
doi: 10.1016/S0079-6123(08)60041-2
pmcid: 6635199
Little, J. W., Ditunno, J. F., Stiens, S. A. & Harris, R. M. Incomplete spinal cord injury: neuronal mechanisms of motor recovery and hyperreflexia. Arch. Phys. Med. Rehabil. 80, 587–599 (1999).
doi: 10.1016/S0003-9993(99)90204-6
pmcid: 10326926