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

We have used a combination of quail-chick fate-mapping techniques and dye labelling to investigate the development of the avian cerebellum. Using Hoxa2 as a guide for the microsurgical construction of quail-chick chimaeras, we show that the caudal boundary of the presumptive cerebellum at E6 maps to the caudal boundary of rhombomere 1. By fate mapping the dorsoventral axis of rhombomere 1, we demonstrate that granule cell precursors are generated at the rhombic lip together with neurons of the lateral pontine nucleus. DiI-labelling of cerebellum explants reveals that external germinal layer precursors have a characteristic unipolar morphology and undergo an orientated, active migration away from the rhombic lip, which is apparently independent of either glial or axon guidance or ‘chain’ formation.

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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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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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Visual Suppression of Vestibular Nystagmus after Cerebellar Lesions

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348947508400306 ◽

1975 ◽

Vol 84 (3) ◽

pp. 318-326 ◽

Cited By ~ 20

Author(s):

Setsuko Takemori

Keyword(s):

Visual System ◽

Cerebellar Cortex ◽

Dentate Nucleus ◽

Complete Loss ◽

Vestibular Nystagmus ◽

Short Term ◽

Vestibular Reflexes ◽

Ipsilateral Side ◽

Visual Suppression ◽

Cerebellar Lesions

Visual suppression of calorically induced vestibular nystagmus was observed following discrete lesions of various structures in the cerebellum. Unilateral lesions of the flocculus resulted in a complete loss or a significant reduction in visual suppression when the quick phase of the nystagmus was directed to the ipsilateral side of the lesions, and bilateral flocculus lesions caused a bilateral loss of suppression. Nodulus lesions resulted in a loss of suppression, and this loss tended to recover in time. Lesions of the dentate nucleus resulted in a very short term loss of suppression. Extirpation or lesions of the uvula, vermis, para-flocculus, cerebellar cortex, or the fastigial or interpositus nuclei had no observed effect on the visual suppression of vestibular nystagmus. The results of this study suggest that the flocculus and nodulus function as intermediators through which the visual system can modify or alter vestibular reflexes. Also, this phenomenon, that is, loss of visual suppression after the flocculus and nodulus lesion, is very useful to diagnose the localized lesion in the cerebellum.

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Morphological changes associated with chronic cerebellar stimulation in the human

Journal of Neurosurgery ◽

10.3171/jns.1979.51.4.0510 ◽

1979 ◽

Vol 51 (4) ◽

pp. 510-520 ◽

Cited By ~ 13

Author(s):

Lee T. Robertson ◽

Robert S. Dow ◽

Irving S. Cooper ◽

Laurence F. Levy

Keyword(s):

Brain Stem ◽

Cerebellar Cortex ◽

Dentate Nucleus ◽

Neuronal Damage ◽

Morphological Changes ◽

Electrode Array ◽

Cortical Surface ◽

Electrode Arrays ◽

Caudal Portion ◽

Cerebellar Stimulation

✓ The histopathology associated with chronic cerebellar stimulation is described for three human cerebellum and brain-stem specimens obtained at autopsy. The specimens were from three severely epileptic patients who received cerebellar stimulation at 10 Hz for 6½ to 15 months. The electrode arrays were completely encapsulated with loose connective tissue that included a proliferation of capillaries, an infiltration of lymphocytes, and an occasional macrophage. The capsule of one of the specimens was tightly adherent to the underlying cerebellar cortex, which may have been caused by some trauma during the surgical placement of the electrodes. Severe injury of the cerebellar cortex was generally confined to between 1 and 2 mm directly beneath the electrode array, and included thinning of the molecular layer, and loss of most Purkinje cells, interneurons, and associated fibers. Abnormal Purkinje cell dendritic patterns and loss of climbing fibers were evident 3 to 4 mm from the cortical surface. At a depth of 5 to 6 mm, there was no distinction from the nonstimulated areas. However, in all specimens the most severe changes, including a complete loss of the neuropil, were evident at the caudal border of the electrode array underlying the connecting wires. A calculation of the amount of severe and very severe neuronal damage for two specimens revealed that 1.2% and 3.1% of the total cortical surface was injured by this neuroprosthesis. Neuropathological changes were also evident in the dentate nucleus and the brain stem. Areas of the dentate nucleus that were close to regions of very severe cortical damage showed marked degenerative changes. Retrograde degeneration was evident primarily within the caudal portion of the medial accessory olivary nucleus.

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