Cerebellar Purkinje Cells Control Posture in Larval Zebrafish (Danio rerio) DOI Creative Commons
Franziska Auer, Katherine Nardone, Kōji Matsuda

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 14, 2023

Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions posture. However, the combined complexity terrestrial locomotion and rodent cerebellum motivate new approaches perturb function simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) describe role Purkinje cells - output neurons cortex as larval zebrafish swam depth. We achieved both bidirectional control (activation ablation) while performing quantitative high-throughput assessment posture locomotion. Activation modified pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis fin-body coordination responsible for climbs. Postural disruption was more widespread older larvae, offering window into emergent roles developing Finally, found that activity could individually collectively encode tilt direction, key feature neurons. Our findings delineate an expected vestibular sensation zebrafish, establishing validity TRPV1/capsaicin-mediated perturbations simple, genetically-tractable vertebrate. Moreover, by comparing cell time, uncover signatures emerging across early development. This takes major step towards understanding ancestral regulating maturation.

Language: Английский

Cerebellar control of targeted tongue movements DOI Creative Commons
Lorenzo Bina,

Camilla Ciapponi,

Si‐yang Yu

et al.

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 26, 2025

Abstract The cerebellum is critical for coordinating movements related to eating, drinking and swallowing, all of which require proper control the tongue. Cerebellar Purkinje cells can encode tongue movements, but it unclear how their simple spikes complex induce changes in shape that contribute goal‐directed movements. To study these relations, we recorded stimulated vermis hemispheres mice during spontaneous licking from a stationary or moving water spout. We found rhythmic with both spikes. Increased spike firing protrusion induces ipsiversive bending Unexpected target location trigger alter subsequent licks, adjusting trajectory. Furthermore, observed increased behavioural state at start end bouts. Using machine learning, confirmed alterations cell activity accompany licking, different often exerting heterogeneous encoding schemes. Our data highlight directional movement paramount cerebellar function modulation are complementary acquisition execution sensorimotor coordination. These results bring us closer understanding clinical implications disorders swallowing. image Key points When drinking, make directed towards source. fire rhythmically tune position source affects direction report also adjust right direction.

Language: Английский

Citations

1
Distribution and functional significance of KLF15 in mouse cerebellum DOI Creative Commons
Dan Li,

Shuijing Cao,

Yanrong Chen

et al.

Molecular Brain, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 21, 2025

Abstract Kruppel-like factor 15 (KLF15), a member of the KLF family, is closely involved in many biological processes. However, mechanism by which KLF15 regulates neural development still unclear. Considering complexity and importance network development, this study, we investigated potent regulatory role development. was detected highly expressed cerebellum enriched Purkinje cells, with significant increase expression between 20 days Knockdown led to loss cells impaired motility mice. Therefore, our study aims elucidate relationship mice, may provide new research idea for developmental mouse cerebellum.

Language: Английский

Citations

0
Pathological Mechanisms of Motor Dysfunction in Familial Danish Dementia: Insights from a Knock-In Rat Model DOI
Arnab Choudhury, Metin Yeşiltepe, Tammaryn Lashley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 20, 2025

Abstract Familial Danish Dementia (FDD) is a rare autosomal dominant neurodegenerative disorder caused by mutation in the integral membrane protein 2B ( ITM2b ) gene. Clinically, FDD characterized cerebral amyloid angiopathy (CAA), cerebellar ataxia, and dementia. Notably, shares several neuropathological features with Alzheimer’s disease (AD), including CAA, neuroinflammation, neurofibrillary tangles. In this study, we investigate pathological mechanisms linking white matter damage, motor dysfunction using recently developed knock-in (FDD-KI) rat model. This model harbors endogenous Itm2b gene, along an App gene encoding humanized amyloid-β (Aβ). Our analysis revealed substantial vascular (ADan) deposition subpial leptomeningeal vessels of FDD-KI rats, showing age-related increase comparable to that observed human patients. Additionally, Aβ deposits (Aβ-CAA) were present but Aβ-CAA patterns showed some differences between species. Motor function assessments rats demonstrated age-accelerated deficits gait abnormalities, mirroring clinical characteristics To further explore underlying these deficits, examined pathology found myelin disruption axonal fiber loss, consistent postmortem pathology. Cerebellar demyelination appeared be driven marked increased microglial/macrophage activation response deposition. extravascular fibrinogen leakage, indicating widespread permeability both gray matter, surrounding amyloid-positive aged cerebellum. These findings suggest first animal recapitulate key patients, ADan- Aβ-type lesions—pathologies may underlie impairments seen disease.

Language: Английский

Citations

0
Cerebellar Pathology in Forensic and Clinical Neuroscience DOI
Azhagu Madhavan Sivalingam,

Darshitha D Sureshkumar

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102697 - 102697

Published: Feb. 1, 2025

Language: Английский

Citations

0
Distribution and Functional Significance of KLF15 in Mouse Cerebellum DOI Creative Commons
Dan Li,

Shuijing Cao,

Yanrong Chen

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 14, 2024

Abstract Kruppel-like factor 15 (KLF15), a member of the KLF family, is closely involved in many biological processes. However, mechanism by which KLF15 regulates neural development still unclear. Considering complexity and importance network development, this study, we investigated potent regulatory role development. was detected highly expressed cerebellum enriched Purkinje cells, with significant increase expression between 15–20 days Knockdown led to loss cells impaired motility mice. Therefore, our study aims elucidate relationship mice, may provide new research idea for developmental mouse cerebellum.

Language: Английский

Citations

0
Cerebellar Purkinje Cells Control Posture in Larval Zebrafish (Danio rerio) DOI Creative Commons
Franziska Auer, Katherine Nardone, Kōji Matsuda

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 14, 2023

Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions posture. However, the combined complexity terrestrial locomotion and rodent cerebellum motivate new approaches perturb function simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) describe role Purkinje cells - output neurons cortex as larval zebrafish swam depth. We achieved both bidirectional control (activation ablation) while performing quantitative high-throughput assessment posture locomotion. Activation modified pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis fin-body coordination responsible for climbs. Postural disruption was more widespread older larvae, offering window into emergent roles developing Finally, found that activity could individually collectively encode tilt direction, key feature neurons. Our findings delineate an expected vestibular sensation zebrafish, establishing validity TRPV1/capsaicin-mediated perturbations simple, genetically-tractable vertebrate. Moreover, by comparing cell time, uncover signatures emerging across early development. This takes major step towards understanding ancestral regulating maturation.

Language: Английский

Citations

1