What Does Low-Intensity rTMS Do to the Cerebellum?

N. Morellini, S. Grehl, A. Tang, Jennifer Rodger, J. Mariani, A.M. Lohof, R.M. Sherrard

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    © 2014, Springer Science+Business Media New York. Non-invasive stimulation of the human cerebellum, such as by transcranial magnetic stimulation (TMS), is increasingly used to investigate cerebellar function and identify potential treatment for cerebellar dysfunction. However, the effects of TMS on cerebellar neurons remain poorly defined. We applied low-intensity repetitive TMS (LI-rTMS) to the mouse cerebellum in vivo and in vitro and examined the cellular and molecular sequelae. In normal C57/Bl6 mice, 4 weeks of LI-rTMS using a complex biomimetic high-frequency stimulation (BHFS) alters Purkinje cell (PC) dendritic and spine morphology; the effects persist 4 weeks after the end of stimulation. We then evaluated whether LI-rTMS could induce climbing fibre (CF) reinnervation to denervated PCs. After unilateral pedunculotomy in adult mice and 2 weeks sham or BHFS stimulation, VGLUT2 immunohistochemistry was used to quantify CF reinnervation. In contrast to sham, LI-rTMS induced CF reinnervation to the denervated hemicerebellum. To examine potential mechanisms underlying the LI-rTMS effect, we verified that BHFS could induce CF reinnervation using our in vitro olivocerebellar explants in which denervated cerebellar tissue is co-cultured adjacent to intact cerebella and treated with brain-derived neurotrophic factor (BDNF) (as a positive control), sham or LI-rTMS for 2 weeks. Compared with sham, BDNF and BHFS LI-rTMS significantly increased CF reinnervation, without additive effect. To identify potential underlying mechanisms, we examined intracellular calcium flux during the 10-min stimulation. Complex high-frequency stimulation increased intracellular calcium by release from intracellular stores. Thus, even at low intensity, rTMS modifies PC structure and induces CF reinnervation.
    Original languageEnglish
    Pages (from-to)23-26
    JournalCerebellum
    Volume14
    Issue number1
    DOIs
    Publication statusPublished - 2015

    Fingerprint

    Biomimetics
    Cerebellum
    Transcranial Magnetic Stimulation
    Purkinje Cells
    Brain-Derived Neurotrophic Factor
    Calcium
    Cerebellar Diseases
    Dendritic Spines
    Immunohistochemistry
    Neurons
    In Vitro Techniques
    Therapeutics

    Cite this

    Morellini, N., Grehl, S., Tang, A., Rodger, J., Mariani, J., Lohof, A. M., & Sherrard, R. M. (2015). What Does Low-Intensity rTMS Do to the Cerebellum? Cerebellum, 14(1), 23-26. https://doi.org/10.1007/s12311-014-0617-9
    Morellini, N. ; Grehl, S. ; Tang, A. ; Rodger, Jennifer ; Mariani, J. ; Lohof, A.M. ; Sherrard, R.M. / What Does Low-Intensity rTMS Do to the Cerebellum?. In: Cerebellum. 2015 ; Vol. 14, No. 1. pp. 23-26.
    @article{9b814a9825e04b26b30a18de06ca9e2b,
    title = "What Does Low-Intensity rTMS Do to the Cerebellum?",
    abstract = "{\circledC} 2014, Springer Science+Business Media New York. Non-invasive stimulation of the human cerebellum, such as by transcranial magnetic stimulation (TMS), is increasingly used to investigate cerebellar function and identify potential treatment for cerebellar dysfunction. However, the effects of TMS on cerebellar neurons remain poorly defined. We applied low-intensity repetitive TMS (LI-rTMS) to the mouse cerebellum in vivo and in vitro and examined the cellular and molecular sequelae. In normal C57/Bl6 mice, 4 weeks of LI-rTMS using a complex biomimetic high-frequency stimulation (BHFS) alters Purkinje cell (PC) dendritic and spine morphology; the effects persist 4 weeks after the end of stimulation. We then evaluated whether LI-rTMS could induce climbing fibre (CF) reinnervation to denervated PCs. After unilateral pedunculotomy in adult mice and 2 weeks sham or BHFS stimulation, VGLUT2 immunohistochemistry was used to quantify CF reinnervation. In contrast to sham, LI-rTMS induced CF reinnervation to the denervated hemicerebellum. To examine potential mechanisms underlying the LI-rTMS effect, we verified that BHFS could induce CF reinnervation using our in vitro olivocerebellar explants in which denervated cerebellar tissue is co-cultured adjacent to intact cerebella and treated with brain-derived neurotrophic factor (BDNF) (as a positive control), sham or LI-rTMS for 2 weeks. Compared with sham, BDNF and BHFS LI-rTMS significantly increased CF reinnervation, without additive effect. To identify potential underlying mechanisms, we examined intracellular calcium flux during the 10-min stimulation. Complex high-frequency stimulation increased intracellular calcium by release from intracellular stores. Thus, even at low intensity, rTMS modifies PC structure and induces CF reinnervation.",
    author = "N. Morellini and S. Grehl and A. Tang and Jennifer Rodger and J. Mariani and A.M. Lohof and R.M. Sherrard",
    year = "2015",
    doi = "10.1007/s12311-014-0617-9",
    language = "English",
    volume = "14",
    pages = "23--26",
    journal = "The Cerebellum",
    issn = "1473-4222",
    publisher = "Springer",
    number = "1",

    }

    Morellini, N, Grehl, S, Tang, A, Rodger, J, Mariani, J, Lohof, AM & Sherrard, RM 2015, 'What Does Low-Intensity rTMS Do to the Cerebellum?' Cerebellum, vol. 14, no. 1, pp. 23-26. https://doi.org/10.1007/s12311-014-0617-9

    What Does Low-Intensity rTMS Do to the Cerebellum? / Morellini, N.; Grehl, S.; Tang, A.; Rodger, Jennifer; Mariani, J.; Lohof, A.M.; Sherrard, R.M.

    In: Cerebellum, Vol. 14, No. 1, 2015, p. 23-26.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - What Does Low-Intensity rTMS Do to the Cerebellum?

    AU - Morellini, N.

    AU - Grehl, S.

    AU - Tang, A.

    AU - Rodger, Jennifer

    AU - Mariani, J.

    AU - Lohof, A.M.

    AU - Sherrard, R.M.

    PY - 2015

    Y1 - 2015

    N2 - © 2014, Springer Science+Business Media New York. Non-invasive stimulation of the human cerebellum, such as by transcranial magnetic stimulation (TMS), is increasingly used to investigate cerebellar function and identify potential treatment for cerebellar dysfunction. However, the effects of TMS on cerebellar neurons remain poorly defined. We applied low-intensity repetitive TMS (LI-rTMS) to the mouse cerebellum in vivo and in vitro and examined the cellular and molecular sequelae. In normal C57/Bl6 mice, 4 weeks of LI-rTMS using a complex biomimetic high-frequency stimulation (BHFS) alters Purkinje cell (PC) dendritic and spine morphology; the effects persist 4 weeks after the end of stimulation. We then evaluated whether LI-rTMS could induce climbing fibre (CF) reinnervation to denervated PCs. After unilateral pedunculotomy in adult mice and 2 weeks sham or BHFS stimulation, VGLUT2 immunohistochemistry was used to quantify CF reinnervation. In contrast to sham, LI-rTMS induced CF reinnervation to the denervated hemicerebellum. To examine potential mechanisms underlying the LI-rTMS effect, we verified that BHFS could induce CF reinnervation using our in vitro olivocerebellar explants in which denervated cerebellar tissue is co-cultured adjacent to intact cerebella and treated with brain-derived neurotrophic factor (BDNF) (as a positive control), sham or LI-rTMS for 2 weeks. Compared with sham, BDNF and BHFS LI-rTMS significantly increased CF reinnervation, without additive effect. To identify potential underlying mechanisms, we examined intracellular calcium flux during the 10-min stimulation. Complex high-frequency stimulation increased intracellular calcium by release from intracellular stores. Thus, even at low intensity, rTMS modifies PC structure and induces CF reinnervation.

    AB - © 2014, Springer Science+Business Media New York. Non-invasive stimulation of the human cerebellum, such as by transcranial magnetic stimulation (TMS), is increasingly used to investigate cerebellar function and identify potential treatment for cerebellar dysfunction. However, the effects of TMS on cerebellar neurons remain poorly defined. We applied low-intensity repetitive TMS (LI-rTMS) to the mouse cerebellum in vivo and in vitro and examined the cellular and molecular sequelae. In normal C57/Bl6 mice, 4 weeks of LI-rTMS using a complex biomimetic high-frequency stimulation (BHFS) alters Purkinje cell (PC) dendritic and spine morphology; the effects persist 4 weeks after the end of stimulation. We then evaluated whether LI-rTMS could induce climbing fibre (CF) reinnervation to denervated PCs. After unilateral pedunculotomy in adult mice and 2 weeks sham or BHFS stimulation, VGLUT2 immunohistochemistry was used to quantify CF reinnervation. In contrast to sham, LI-rTMS induced CF reinnervation to the denervated hemicerebellum. To examine potential mechanisms underlying the LI-rTMS effect, we verified that BHFS could induce CF reinnervation using our in vitro olivocerebellar explants in which denervated cerebellar tissue is co-cultured adjacent to intact cerebella and treated with brain-derived neurotrophic factor (BDNF) (as a positive control), sham or LI-rTMS for 2 weeks. Compared with sham, BDNF and BHFS LI-rTMS significantly increased CF reinnervation, without additive effect. To identify potential underlying mechanisms, we examined intracellular calcium flux during the 10-min stimulation. Complex high-frequency stimulation increased intracellular calcium by release from intracellular stores. Thus, even at low intensity, rTMS modifies PC structure and induces CF reinnervation.

    U2 - 10.1007/s12311-014-0617-9

    DO - 10.1007/s12311-014-0617-9

    M3 - Article

    VL - 14

    SP - 23

    EP - 26

    JO - The Cerebellum

    JF - The Cerebellum

    SN - 1473-4222

    IS - 1

    ER -