Neurostructural changes and declining sensorimotor function due to cerebellar cortical degeneration

2021 ◽  
Author(s):  
Rossitza Draganova ◽  
Viktor Pfaffenrot ◽  
Katharina M Steiner ◽  
Sophia L Göricke ◽  
Naveen Elangovan ◽  
...  
Keyword(s):  
Cerebellar Cortex ◽  
Cortical Neurons ◽  
Motor Performance ◽  
Premotor Cortex ◽  
Gray Matter Volume ◽  
Cerebellar Nuclei ◽  
Fine Motor ◽  
Deep Cerebellar Nuclei ◽  
Compensatory Response ◽  
Cerebellar Cortical Degeneration

Neurodegeneration of the cerebellum progresses over years and primarily affects cerebellar cortex. It leads to a progressive loss of control and coordination of gait, posture, speech, fine motor and oculomotor function. Yet, little is known how the cerebro-cerebellar network compensates for the loss in cerebellar cortical neurons. To address this knowledge gap we examined 30 people with cerebellar cortical degeneration and a group of 30 healthy controls. We assessed visuomotor performance during a forearm-pointing task to 10°, 25° and 50° targets. In addition, using MRI imaging, we determined neurodegenerative-induced changes in gray matter volume (GMV) in the cerebro-cerebellar network and correlated them to markers of motor performance. The main results are as follows: First, the relative joint position error (RJPE) during pointing was significantly greater in the ataxia group for all targets confirming the expected motor control deficit. Second, in the ataxia group GMV was significantly reduced in cerebellar cortex but increased in the deep cerebellar nuclei. Motor error (RJPE) correlated negatively with decreased cerebellar GMV, but positively with increased GMV in SMA and premotor cortex. GMV of the deep cerebellar nuclei did not correlate significantly with markers of motor performance. We discuss, whether the GMV changes in the cerebellar output nuclei and the extracerebellar efferent targets in secondary motor cortex can be understood as a central compensatory response to the neurodegeneration of the cerebellar cortex.

Cerebellar Grafts Partially Reverse Amino Acid Receptor Changes Observed in the Cerebellum of Mice with Hereditary Ataxia: Quantitative Autoradiographic Studies

1997 ◽  
Vol 6 (3) ◽  
pp. 347-359
Author(s):  
Kalliope Stasi ◽  
Adamantia Mitsacos ◽  
Lazaros C. Triarhou ◽  
Elias D. Kouvelas
Keyword(s):  
Nmda Receptors ◽  
Cerebellar Cortex ◽  
Binding Sites ◽  
Molecular Layer ◽  
Cerebellar Nuclei ◽  
Granule Cell Layer ◽  
Wild Type ◽  
Hereditary Ataxia ◽  
Deep Cerebellar Nuclei ◽  
Muscimol Binding

We used quantitative autoradiography of [3H]CNQX (200 nM), [3H]muscimol (13 nM), and [3H]flunitrazepam (10 nM) binding to study the distribution of non-NMDA and GABAA receptors in the cerebellum of pcd mutant mice with unilateral cerebellar grafts. Nonspecific binding was determined by incubation with 1 mM Glu, 200 μM GABA, or 1 μM clonazepam, respectively. Saturation parameters were defined in wild-type and mutant cerebella. In mutants, non-NMDA receptors were reduced by 38% in the molecular layer and by 47% in the granule cell layer. The reduction of non-NMDA receptors in the pcd cerebellar cortex supports their localization on Purkinje cells. [3H] CNQX binding sites were visualized at higher density in grafts that had migrated to the cerebellar cortex of the hosts (4.1 and 11.0 pmol/mg protein, respectively, at 23 and 37 days after grafting) than in grafts arrested intraparen-chymally (2.6 and 6.2 pmol/mg protein, respectively, at 23 and 37 days after grafting). The pattern of expression of non-NMDA receptors in cortical vs. parenchymal grafts suggests a possible regulation of their levels by transacting elements from host parallel fibers. GABAA binding levels in the grafts for both ligands used were similar to normal molecular layer. Binding was increased in the deep cerebellar nuclei of pcd mutants: the increase in [3H]muscimol binding over normal was 215% and the increase in [3H]flunitrazepam binding was 89%. Such increases in the pcd deep cerebellar nuclei may reflect a denervation-induced supersensitivity subsequent to the loss of Purkinje axon terminal innervation. In the deep nuclei of pcd mutants with unilateral cerebellar grafts, [3H]muscimol binding was 31% lower in the grafted side than in the contralateral nongrafted side at 37 days after transplantation; [3H]fluni-trazepam binding was also lower in the grafted side by 15% compared to the nongrafted side. Such changes in GABAA receptors suggest a significant, albeit partial, normalizing trend of cerebellar grafts on the state of postsynaptic supersensitive receptors in the host cerebellar nuclei.

Effects of red nucleus inactivation on burst discharge in turtle cerebellum in vitro: evidence for positive feedback

1996 ◽  
Vol 76 (4) ◽  
pp. 2200-2210 ◽  
Author(s):  
J. Keifer
Keyword(s):  
Cerebellar Cortex ◽  
Positive Feedback ◽  
Red Nucleus ◽  
Cerebellar Nuclei ◽  
Cerebellar Nucleus ◽  
Normal Brain ◽  
Deep Cerebellar Nuclei ◽  
Burst Discharge ◽  
Sustained Discharge

1. In behaving animals the red nucleus produces sustained action potential discharge during movements of the limbs. These bursts are thought to encode parameters of movement and thereby represent motor commands. Similar bursts can be recorded in the in vitro brain stem-cerebellum from the turtle. In this preparation, sustained discharge of red nucleus neurons was postulated to be generated by N-methyl-D-aspartate-mediated cellular mechanisms acting in combination with positive feedback in a recurrent cerebellorubral network. The present study was designed to test this positive feedback hypothesis. During recording of sustained discharge in the deep cerebellar nuclei and cortex, the red nucleus was reversibly inactivated by microinjection. The positive feedback hypothesis would be supported if activity in the cerebellum was attenuated by inactivation of the red nucleus. A nonrecurrent source of excitation would have to be postulated if cerebellar activity was unaffected. 2. Extracellular single-unit recordings were made from neurons in the deep cerebellar nuclei, cerebellar cortex, and vestibular nuclei. Burst discharges were evoked by brief electrical stimuli applied to the spinal cord that activated sensory structures. During inactivation of the red nucleus, sensory projections to the cerebellum that may evoke burst discharge were unaffected. Pressure microinjections of cobalt, lidocaine, gamma-aminobutyric acid (GABA), or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were used to reversibly inactivate the red nucleus. Saline injections were also tested. 3. Sustained discharge of all neurons recorded in the lateral cerebellar nucleus was greatly attenuated or blocked completely by injection of the pharmacological agents into the red nucleus. These effects were reversible. Of the recordings in the cerebellar cortex, 63% of these were blocked. All four compounds tested were effective blockers of the bursts, although the effects of GABA were less potent than the others. Saline injections into the red nucleus showed no effect. Burst discharges of single units recorded in either the medial cerebellar nucleus or the vestibular complex, which do not receive input from the red nucleus, showed no effect of red nucleus inactivation. 4. The results showed that sustained discharge in the cerebellum was significantly attenuated by inactivation of the red nucleus even though sensory input that may trigger the bursts was intact. These data support the hypothesis that sustained discharge in the cerebellorubral circuit is generated by a distributed neuronal network that uses positive feedback. The results have implications for mechanisms underlying normal brain function and some motor disorders.

Dynamic Synchronization of Purkinje Cell Simple Spikes

2006 ◽  
Vol 96 (6) ◽  
pp. 3485-3491 ◽  
Author(s):  
Soon-Lim Shin ◽  
Erik De Schutter
Keyword(s):  
Purkinje Cell ◽  
Firing Rate ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Cerebellar Nuclei ◽  
Temporal Coding ◽  
Sharp Peak ◽  
Deep Cerebellar Nuclei

Purkinje cells (PCs) integrate all computations performed in the cerebellar cortex to inhibit neurons in the deep cerebellar nuclei (DCN). Simple spikes recorded in vivo from pairs of PCs separated by <100 μm are known to be synchronized with a sharp peak riding on a broad peak, but the significance of this finding is unclear. We show that the sharp peak consists exclusively of simple spikes associated with pauses in firing. The broader, less precise peak was caused by firing-rate co-modulation of faster firing spikes. About 13% of all pauses were synchronized, and these pauses had a median duration of 20 ms. As in vitro studies have reported that synchronous pauses can reliably trigger spikes in DCN neurons, we suggest that the subgroup of spikes causing the sharp peak is important for precise temporal coding in the cerebellum.

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