title: Restoration of contralateral representation in the mouse somatosensory cortex after crossing nerve transfer.
abstract: Avulsion of spinal nerve roots in the brachial plexus (BP) can be repaired by crossing nerve transfer via a nerve graft to connect injured nerve ends to the BP contralateral to the lesioned side. Sensory recovery in these patients suggests that the contralateral primary somatosensory cortex (S1) is activated by afferent inputs that bypassed to the contralateral BP. To confirm this hypothesis, the present study visualized cortical activity after crossing nerve transfer in mice through the use of transcranial flavoprotein fluorescence imaging. In naïve mice, vibratory stimuli applied to the forepaw elicited localized fluorescence responses in the S1 contralateral to the stimulated side, with almost no activity in the ipsilateral S1. Four weeks after crossing nerve transfer, forepaw stimulation in the injured and repaired side resulted in cortical responses only in the S1 ipsilateral to the stimulated side. At eight weeks after crossing nerve transfer, forepaw stimulation resulted in S1 cortical responses of both hemispheres. These cortical responses were abolished by cutting the nerve graft used for repair. Exposure of the ipsilateral S1 to blue laser light suppressed cortical responses in the ipsilateral S1, as well as in the contralateral S1, suggesting that ipsilateral responses propagated to the contralateral S1 via cortico-cortical pathways. Direct high-frequency stimulation of the ipsilateral S1 in combination with forepaw stimulation acutely induced S1 bilateral cortical representation of the forepaw area in naïve mice. Cortical responses in the contralateral S1 after crossing nerve transfer were reduced in cortex-restricted heterotypic GluN1 (NMDAR1) knockout mice. Functional bilateral cortical representation was not clearly observed in genetically manipulated mice with impaired cortico-cortical pathways between S1 of both hemispheres. Taken together, these findings strongly suggest that activity-dependent potentiation of cortico-cortical pathways has a critical role for sensory recovery in patients after crossing nerve transfer.
authors.affiliation: Department of Neurophysiology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Yamashita
authors.forename: Shanlin
authors.initials: S
authors.lastname: Chen
authors.forename: Seiji
authors.initials: S
authors.lastname: Komagata
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Hishida
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwasato
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yagi
authors.forename: Naoto
authors.initials: N
authors.lastname: Endo
authors.forename: Minoru
authors.initials: M
authors.lastname: Shibata
authors.forename: Katsuei
authors.initials: K
authors.lastname: Shibuki
mesh_terms: D000818:Animals; D001917:Brachial Plexus / Q000601:surgery*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D008297:Male; D040542:Mechanotransduction, Cellular; D008475:Median Nerve / Q000502:physiology / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009416:Nerve Regeneration; D016067:Nerve Transfer; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012584:Sciatic Nerve / Q000637:transplantation; D013003:Somatosensory Cortex / Q000033:anatomy & histology / Q000502:physiology*; D014459:Ulnar Nerve / Q000502:physiology / Q000601:surgery
chemical_list: D015820:Cadherins; D016194:Receptors, N-Methyl-D-Aspartate