Biology subjects

Hoedemaker, H.

Publications and source records attributed to Hoedemaker, H..

3 recordsLinked to original sources

bioRxiv2026

Motor experience leads to structural changes in the adult male mouse inferior olive

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.

neuroscience↗

bioRxiv2022

How inhibitory and excitatory inputs gate output of the inferior olive

The inferior olive provides the climbing fibers to Purkinje cells in the cerebellar cortex, where they elicit all-or-none complex spikes and control major forms of plasticity. Given their important role in both short-term and long-term coordination of cerebellum-dependent behaviors, it is paramount to understand the factors that determine the output of olivary neurons. Here, we investigate how the inhibitory and excitatory inputs to the olivary neurons interact with each other, generating spiking patterns of olivary neurons that ride on their intrinsic oscillations. Using dual color optogenetic stimulation and whole cell recordings we demonstrate how intervals between the inhibitory input from the cerebellar nuclei and excitatory input from the mesodiencephalic junction affect phase and gain of the olivary output at both the sub- and suprathreshold level. When the excitatory input is activated approximately 50 ms after the inhibitory input, the phase of the intrinsic oscillations becomes remarkably unstable and the excitatory input can hardly generate any olivary spike. Instead, when the excitatory input is activated approximately 150 ms after the inhibitory input, the excitatory input can optimally drive olivary spiking, riding on top of the first cycle of the subthreshold oscillations that have been powerfully reset by the preceding inhibitory input. Simulations of a large-scale network model of the inferior olive highlight to what extent the synaptic interactions penetrate in the neuropil, generating quasi-oscillatory spiking patterns in large parts of the olivary subnuclei, the size of which also depends on the relative timing of the inhibitory and excitatory inputs.

neuroscience↗

bioRxiv2019

NINscope: a versatile miniscope for multi-region circuit investigations

Miniaturized fluorescence microscopes (miniscopes) have been instrumental to monitor neural activity during unrestrained behavior and their open-source versions have helped to distribute them at an affordable cost. Generally, the footprint and weight of open-source miniscopes is sacrificed for added functionality. Here, we present NINscope: a light-weight, small footprint, open-source miniscope that incorporates a high-sensitivity image sensor, an inertial measurement unit (IMU), and an LED driver for an external optogenetic probe. We highlight the advantages of NINscope by performing the first simultaneous cellular resolution (dual scope) recordings from cerebellum and cerebral cortex in unrestrained mice, revealing that the activity of both regions generally precedes the onset of behavioral acceleration. We further demonstrate the optogenetic stimulation capabilities of NINscope and show that cerebral cortical activity can be driven strongly by cerebellar stimulation. To validate the performance of our miniscope to image from deep-brain regions, we recorded in the dorsal striatum and, using the IMU to assess turning movements, replicate previous studies that show encoding of action space in this subcortical region. Finally, we combine optogenetic stimulation of distinct cortical regions projecting to the dorsal striatum, to probe functional connectivity. In combination with cross-platform control software, NINscope is a versatile addition to the expanding toolbox of open-source miniscopes and will aid multi-region circuit investigations during unrestrained behavior.

neuroscience↗