PMID- 25346177 OWN - NLM STAT- MEDLINE DCOM- 20151023 LR - 20220317 IS - 1473-4230 (Electronic) IS - 1473-4222 (Linking) VI - 14 IP - 1 DP - 2015 Feb TI - What does low-intensity rTMS do to the cerebellum? PG - 23-6 LID - 10.1007/s12311-014-0617-9 [doi] AB - 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. FAU - Morellini, N AU - Morellini N AD - UMR8256 Biological Adaptation and Ageing, IBPS-B2A, Sorbonne Universites UPMC-Univ Paris 6 and CNRS, 75005, Paris, France. FAU - Grehl, S AU - Grehl S FAU - Tang, A AU - Tang A FAU - Rodger, J AU - Rodger J FAU - Mariani, J AU - Mariani J FAU - Lohof, A M AU - Lohof AM FAU - Sherrard, R M AU - Sherrard RM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Cerebellum JT - Cerebellum (London, England) JID - 101089443 SB - IM MH - Animals MH - Cerebellum/pathology/*physiopathology MH - Purkinje Cells/pathology/physiology MH - *Transcranial Magnetic Stimulation/methods EDAT- 2014/10/28 06:00 MHDA- 2015/10/24 06:00 CRDT- 2014/10/28 06:00 PHST- 2014/10/28 06:00 [entrez] PHST- 2014/10/28 06:00 [pubmed] PHST- 2015/10/24 06:00 [medline] AID - 10.1007/s12311-014-0617-9 [doi] PST - ppublish SO - Cerebellum. 2015 Feb;14(1):23-6. doi: 10.1007/s12311-014-0617-9.