Motor experience leads to structural changes in the adult male mouse inferior olive
- 1Okinawa Institute of Science and Technology
Abstract
The activity of the inferior olive (IO), conveyed to the cerebellar cortex via climbing fibers and manifesting as the complex spikes (CSs) in Purkinje neurons, is at the core of major theories of cerebellar function and motor learning. While the computational meaning of the CSs remains under intense debate, it is well accepted that changes in their occurrence and timing play a critical role in guiding cerebellar plasticity. However, it has not been examined whether the plastic processes leading to these changes in cerebellar CS activity are expressed in the IO, or whether they are entirely caused by changes in brain structures upstream of the climbing fibers, including the cerebellar nuclei. Here, we examine whether prolonged, kinematically challenging motor experience can lead to detectable changes in the IO network structure that could underlie shifts in cerebellar CS activity. As the IO neurons communicate exclusively via electrical synapses (gap junctions) residing on dendritic structures, we hypothesized that if long-term increases in electrical coupling related to the insertion of new gap junctions occur in response to novel motor experiences, morphological changes in the dendrites would also be expected. To investigate this, we quantitatively characterized the geometry of the IO neuropil revealed by immunohistochemical staining in adult male mice. We found that the neuropil structure varies across olivary subnuclei in naive animals, possibly underlying known differences in cerebellar complex spike co-activation patterns. Geometrical measures related to structural complexity also revealed that exposing the animals to a challenging high-speed treadmill running task requiring full-body coordination led to localized changes suggestive of increased network connectivity. In addition, the density of immunofluorescence puncta labeling Cx36 increased in the same regions, supporting the notion that exposure to contexts where novel motor skills need to be acquired may lead to changes in the clustering strength among IO neurons and thereby restructuring of the olivo-cerebellar micromodules. To our knowledge, this is the first report of experience-related plasticity within the IO, calling for renewed attention to the role of the IO in olivocerebellar function.
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BibTeX
@misc{turkki2026motor,
title = {{Motor experience leads to structural changes in the adult male mouse inferior olive}},
author = {T. H. Turkki and S. Dubois and H. Hoedemaker and T. Salamovska and B. M. Ignatowska-Jankowska and M. Y. Uusisaari},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.747181},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.747181v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Motor experience leads to structural changes in the adult male mouse inferior olive
AU - T. H. Turkki
AU - S. Dubois
AU - H. Hoedemaker
AU - T. Salamovska
AU - B. M. Ignatowska-Jankowska
AU - M. Y. Uusisaari
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.747181
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.747181v1
AB - The activity of the inferior olive (IO), conveyed to the cerebellar cortex via climbing fibers and manifesting as the complex spikes (CSs) in Purkinje neurons, is at the core of major theories of cerebellar function and motor learning. While the computational meaning of the CSs remains under intense debate, it is well accepted that changes in their occurrence and timing play a critical role in guiding cerebellar plasticity. However, it has not been examined whether the plastic processes leading to these changes in cerebellar CS activity are expressed in the IO, or whether they are entirely caused by changes in brain structures upstream of the climbing fibers, including the cerebellar nuclei. Here, we examine whether prolonged, kinematically challenging motor experience can lead to detectable changes in the IO network structure that could underlie shifts in cerebellar CS activity. As the IO neurons communicate exclusively via electrical synapses (gap junctions) residing on dendritic structures, we hypothesized that if long-term increases in electrical coupling related to the insertion of new gap junctions occur in response to novel motor experiences, morphological changes in the dendrites would also be expected. To investigate this, we quantitatively characterized the geometry of the IO neuropil revealed by immunohistochemical staining in adult male mice. We found that the neuropil structure varies across olivary subnuclei in naive animals, possibly underlying known differences in cerebellar complex spike co-activation patterns. Geometrical measures related to structural complexity also revealed that exposing the animals to a challenging high-speed treadmill running task requiring full-body coordination led to localized changes suggestive of increased network connectivity. In addition, the density of immunofluorescence puncta labeling Cx36 increased in the same regions, supporting the notion that exposure to contexts where novel motor skills need to be acquired may lead to changes in the clustering strength among IO neurons and thereby restructuring of the olivo-cerebellar micromodules. To our knowledge, this is the first report of experience-related plasticity within the IO, calling for renewed attention to the role of the IO in olivocerebellar function.
ER -