
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Июнь 14, 2024
Язык: Английский
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Июнь 14, 2024
Язык: Английский
The Journal of Physiology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 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.
Язык: Английский
Процитировано
1Molecular Brain, Год журнала: 2025, Номер 18(1)
Опубликована: Янв. 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.
Язык: Английский
Процитировано
0Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102697 - 102697
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Апрель 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.
Язык: Английский
Процитировано
0bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown
Опубликована: Сен. 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.
Язык: Английский
Процитировано
1Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Июнь 14, 2024
Язык: Английский
Процитировано
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