Activation of the cerebellar cortex and the dentate nucleus in a prism adaptation fMRI study

Cerebellar lesions and prism adaptation in Macaque monkeys. If a laterally displacing prism is placed in front of one eye of a person or monkey with the other eye occluded, they initially will point to one side of a target that is located directly in front of them. Normally, people and monkeys adapt easily to the displaced vision and correct their aim after a few trials. If the prism then is removed, there is a postadaptation shift in which the subject misses the target and points in the opposite direction for a few trials. We tested five Macaque monkeys for their ability to adapt to a laterally displacing prism and to show the expected postadaptation shift. When tested as normals, all five animals showed the typical pattern of adaptation and postadaptation shift. Like human subjects, the monkeys also showed complete interocular transfer of the adaptation but no transfer of the adaptation between the two arms. When preoperative training and testing was complete, we made lesions of various target areas on the cerebellar cortex. A cerebellar lesion that included the dorsal paraflocculus and uvula abolished completely the normal prism adaptation for the arm ipsilateral to the lesion in one of the five monkeys. The other four animals retained the ability to prism-adapt normally and showed the expected postadaptation shift. In the one case in which the lesion abolished prism adaptation, the damage included Crus I and II, paramedian lobule and the dorsal paraflocculus of the cerebellar hemispheres as well as lobule IX, of the vermis. Thus in this case, the lesion included virtually all the cerebellar cortex that receives mossy-fiber visual information relayed via the pontine nuclei from the cerebral cortex. The other four animals had damage to lobule V, the classical anterior lobe arm area and/or vermian lobules VI/VII, the oculomotor region. When tested postoperatively, some of these animals showed a degree of ataxia equivalent to that of the case in which prism adaptation was affected, but prism adaptation and the postadaptation shift remained normal. We conclude that in addition to its role in long-term motor learning and reflex adaptation, the region of the cerebellum that was ablated also may be a critical site for a short-term motor memory. Prism adaptation seems to involve a region of the cerebellum that receives a mossy-fiber visual error signal and probably a corollary discharge of the movement.

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Evidence for a motor somatotopy in the cerebellar dentate nucleus-An FMRI study in humans

Human Brain Mapping ◽

10.1002/hbm.21400 ◽

2011 ◽

Vol 33 (11) ◽

pp. 2741-2749 ◽

Cited By ~ 37

Author(s):

Michael Küper ◽

Markus Thürling ◽

Roxana Stefanescu ◽

Stefan Maderwald ◽

Johannes Roths ◽

...

Keyword(s):

Dentate Nucleus ◽

Fmri Study ◽

Cerebellar Dentate Nucleus

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Multi-omics integration of the phenome, transcriptome and genome highlights genes and pathways relevant to essential tremor

10.1101/580753 ◽

2019 ◽

Author(s):

Calwing Liao ◽

Faezeh Sarayloo ◽

Daniel Rochefort ◽

Gabrielle Houle ◽

Fulya Akçimen ◽

...

Keyword(s):

Association Study ◽

Essential Tremor ◽

Cerebellar Cortex ◽

Dentate Nucleus ◽

Olfactory Loss ◽

Genome Wide ◽

A Genome ◽

Gated Channel ◽

Rare Genetic Variants ◽

Gene Association Study

AbstractThe genetic factors predisposing to essential tremor (ET), of one of the most common movement disorders, remains largely unknown. While current studies have examined the contribution of both common and rare genetic variants, very few have investigated the ET transcriptome. To understand pathways and genes relevant to ET, we used an RNA sequencing approach to interrogate the transcriptome of two cerebellar regions, the dentate nucleus and cerebellar cortex, in 16 cases and 16 age- and sex-matched controls. Additionally, a phenome-wide association study (pheWAS) of the dysregulated genes was conducted, and a genome-wide gene association study (GWGAS) was done to identify pathways overlapping with the transcriptomic data. We identified several novel dysregulated genes includingCACNA1A, a calcium voltage-gated channel implicated in ataxia. Furthermore, several pathways including axon guidance, olfactory loss, and calcium channel activity were significantly enriched. A subsequent examination of the ET GWGAS data (N=7,154) also flagged genes involved in calcium ion-regulated exocytosis of neurotransmitters to be significantly enriched. Interestingly, the pheWAS identified that the dysregulated gene,SHF, is associated with a blood pressure medication (P=9.3E-08), which is commonly used to reduce tremor in ET patients. Lastly, it is also notable that the dentate nucleus and cerebellar cortex have different transcriptomes, suggesting that different regions of the cerebellum have spatially different transcriptomes.

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Cerebellar inactivation impairs memory of learned prism gaze-reach calibrations

Journal of Neurophysiology ◽

10.1152/jn.01009.2010 ◽

2011 ◽

Vol 105 (5) ◽

pp. 2248-2259 ◽

Cited By ~ 19

Author(s):

Scott A. Norris ◽

Emily N. Hathaway ◽

Jordan A. Taylor ◽

W. Thomas Thach

Keyword(s):

Kainic Acid ◽

Cerebellar Cortex ◽

Dentate Nucleus ◽

Visually Guided ◽

The Gaze ◽

Reach Angle ◽

And Performance ◽

And Storage ◽

Direction Opposite

Three monkeys performed a visually guided reach-touch task with and without laterally displacing prisms. The prisms offset the normally aligned gaze/reach and subsequent touch. Naive monkeys showed adaptation, such that on repeated prism trials the gaze-reach angle widened and touches hit nearer the target. On the first subsequent no-prism trial the monkeys exhibited an aftereffect, such that the widened gaze-reach angle persisted and touches missed the target in the direction opposite that of initial prism-induced error. After 20–30 days of training, monkeys showed long-term learning and storage of the prism gaze-reach calibration: they switched between prism and no-prism and touched the target on the first trials without adaptation or aftereffect. Injections of lidocaine into posterolateral cerebellar cortex or muscimol or lidocaine into dentate nucleus temporarily inactivated these structures. Immediately after injections into cortex or dentate, reaches were displaced in the direction of prism-displaced gaze, but no-prism reaches were relatively unimpaired. There was little or no adaptation on the day of injection. On days after injection, there was no adaptation and both prism and no-prism reaches were horizontally, and often vertically, displaced. A single permanent lesion (kainic acid) in the lateral dentate nucleus of one monkey immediately impaired only the learned prism gaze-reach calibration and in subsequent days disrupted both learning and performance. This effect persisted for the 18 days of observation, with little or no adaptation.

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Cerebellum: Development of the Rhombic Lip, Cerebellar Cortex, Dentate Nucleus

Perinatal Neuropathology ◽

10.1017/9781316671863.023 ◽

2021 ◽

pp. 107-110

Author(s):

Rebecca Folkerth

Keyword(s):

Cerebellar Cortex ◽

Dentate Nucleus ◽

Cerebellum Development ◽

Rhombic Lip

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Axon collaterals of mossy fibers from the pontine nucleus in the cerebellar dentate nucleus

Journal of Neurophysiology ◽

10.1152/jn.1992.67.3.547 ◽

1992 ◽

Vol 67 (3) ◽

pp. 547-560 ◽

Cited By ~ 86

Author(s):

Y. Shinoda ◽

Y. Sugiuchi ◽

T. Futami ◽

R. Izawa

Keyword(s):

Cerebral Cortex ◽

White Matter ◽

Cerebellar Cortex ◽

Dentate Nucleus ◽

Mossy Fibers ◽

Terminal Branch ◽

Axon Collateral ◽

Pontine Nucleus ◽

Axon Collaterals ◽

Stimulation Of

1. Single axons of pontine nucleus neurons (PN axons) receiving cerebral input were stained intra-axonally with horseradish peroxidase (HRP) in the cerebellum of cats. The axonal trajectory of single PN axons was reconstructed from serial sections of the cerebellum and the brain stem. 2. Axons were penetrated in the white matter near the dentate nucleus, and, after electrophysiological identification, PN axons were injected iontophoretically with HRP. The identification criteria for the PN axons were 1) their direct responses to stimulation of the contralateral pontine nucleus (PN), 2) their synaptic activation from the contralateral cerebral cortex, and 3) the decrease in threshold for evoking direct spikes in stimulation of the PN by conditioning stimuli applied in the cerebral cortex. 3. Two hundred thirty-three axons were electrophysiologically identified as PN axons receiving the input from the cerebral cortex. Ninety-six of them were stained successfully with HRP, and reconstructions were made from 40 well-stained PN axons. All of them gave rise to mossy fibers and terminated in the granular layer of the cerebellar cortex as typical mossy fiber rosettes. Out of these, 22 gave axon collaterals to the dentate nucleus. Virtually all of the axon branches observed in the dentate nucleus were axon collaterals of mossy fibers from the PN to the cerebellar cortex. In 7 of these 22 PN axons, cell bodies were retrogradely labeled with HRP, and all of them were found in the contralateral PN. 4. The stained-stem axons arising from the PN ran medially in the pons, crossed the midline, and then ascended dorsocaudally in the branchium pontis. After passing in the white matter anterior to or lateral to the dentate nucleus, they entered into the cerebellar cortex. On their way, one to three axon collaterals were given off from parent axons to the dentate nucleus. The diameter of these collaterals was very thin (mean, 0.6 microns), compared with the large diameter of the parent axons (mean, 2.1 microns). 5. Some axon collaterals were very simple and had only one terminal branch with or without short branchlets, whereas others were more complex, and single axon collaterals ramified before forming a terminal arborization. Axon collaterals of single PN axons mainly spread mediolaterally or dorsoventrally in the frontal plane but had a very narrow rostrocaudal extension. 6. Terminal branches usually bore swellings en passant along their length and one terminal swelling at their end. The number of swellings per axon collateral ranged 23-180 (116 +/- 52, mean +/- SD).(ABSTRACT TRUNCATED AT 400 WORDS)

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