Deconstructing cerebellar development cell by cell DOI Creative Commons
Max J. van Essen, Samuel Nayler, Esther B. E. Becker

et al.

PLoS Genetics, Journal Year: 2020, Volume and Issue: 16(4), P. e1008630 - e1008630

Published: April 16, 2020

The cerebellum is a pivotal centre for the integration and processing of motor sensory information. Its extended development into postnatal period makes this structure vulnerable to variety pathologies, including neoplasia. These properties have prompted intensive investigations that reveal not only developmental mechanisms in common with other regions neuraxis but also unique strategies generate neuronal diversity. How phenotypically distinct cell types emerge rests on understanding how gene expression differences arise spatially temporally coordinated manner from initially homogeneous populations. Increasingly sophisticated fate mapping approaches, culminating genetic-induced mapping, furthered lineage relationships between early- versus later-born cells. Tracing histories cells way coupled analysis patterns has provided insight genetic programmes instruct cellular heterogeneity. A limitation date been bulk cells, which blurs obscures underpin taxonomy cerebellum. This review emphasises recent discoveries, focusing mainly single-cell sequencing mouse parallel human studies elucidate neural progenitor trajectories unprecedented resolution. Complementary functional repair after cerebellar injury are challenging assumptions about stability identities. result wealth new information diversity, implications evolution.

Language: Английский

Human organoids in basic research and clinical applications DOI Creative Commons
Xiaoyan Tang,

Shanshan Wu,

Da Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: May 24, 2022

Abstract Organoids are three-dimensional (3D) miniature structures cultured in vitro produced from either human pluripotent stem cells (hPSCs) or adult (AdSCs) derived healthy individuals patients that recapitulate the cellular heterogeneity, structure, and functions of organs. The advent 3D organoid systems is now possible to allow remarkably detailed observation cell morphogens, maintenance differentiation resemble primary tissues, enhancing potential study both physiology developmental stage. As they similar their original organs carry genetic information, organoids patient hold great promise for biomedical research preclinical drug testing currently used personalized, regenerative medicine, gene repair transplantation therapy. In recent decades, researchers have succeeded generating various types mimicking vivo Herein, we provide an update on current technologies brain, retinal, kidney, liver, lung, gastrointestinal, cardiac, vascularized multi-lineage organoids, discuss differences between PSC- AdSC-derived summarize applications cell-derived laboratory clinic, outline challenges application which would deepen understanding mechanisms development enhance further utility basic clinical studies.

Language: Английский

Citations

240
Spatial and cell type transcriptional landscape of human cerebellar development DOI
Kimberly A. Aldinger, Zachary Thomson,

Ian G. Phelps

et al.

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(8), P. 1163 - 1175

Published: June 17, 2021

Language: Английский

Citations

158
Prediction signals in the cerebellum: Beyond supervised motor learning DOI Creative Commons
Court Hull

eLife, Journal Year: 2020, Volume and Issue: 9

Published: March 24, 2020

While classical views of cerebellar learning have suggested that this structure predominantly operates according to an error-based supervised rule refine movements, emerging evidence suggests the cerebellum may also harness a wider range rules contribute variety behaviors, including cognitive processes. Together, such points broad role for circuits in generating and testing predictions about movement, reward, other non-motor operations. However, expanded view processing raises many new questions how apparent diversity function arises from with striking homogeneity. Hence, review will highlight both current predictive circuit extends beyond error-driven learning, as well open must be addressed unify our understanding function.

Language: Английский

Citations

157
Cognitive-Affective Functions of the Cerebellum DOI Creative Commons
Stephanie Rudolph, Aleksandra Badura, Stefano Lutzu

et al.

Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 43(45), P. 7554 - 7564

Published: Nov. 8, 2023

The cerebellum, traditionally associated with motor coordination and balance, also plays a crucial role in various aspects of higher-order function dysfunction. Emerging research has shed light on the cerebellum's broader contributions to cognitive, emotional, reward processes. influence autonomic further highlights its significance regulating motivational emotional states. Perturbations cerebellar development have been implicated neurodevelopmental disorders, including autism spectrum disorder attention deficit hyperactivity disorder. An increasing appreciation for neuropsychiatric symptoms that arise from dysfunction underscores importance elucidating circuit mechanisms underlie complex interactions between cerebellum other brain regions comprehensive understanding behavior. By briefly discussing new advances mapping affective, autonomic, social processing reviewing neuropathology beyond domain, this Mini-Symposium review aims provide broad perspective intersections limbic health disease.

Language: Английский

Citations

49
Human cerebellar organoids with functional Purkinje cells DOI Creative Commons
Alexander Atamian, Marcella Birtele, Negar Hosseini

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(1), P. 39 - 51.e6

Published: Jan. 1, 2024

Language: Английский

Citations

38
Deep brain stimulation foundations and future trends DOI

Travis S. Tierney

Frontiers in bioscience, Journal Year: 2017, Volume and Issue: 23(1), P. 162 - 182

Published: Sept. 22, 2017

Deep brain stimulation (DBS) has emerged as a revolutionary treatment option for essential tremor (ET), Parkinson's disease (PD), idiopathic dystonia, and severe obsessive-compulsive disorder (OCD). This article reviews the historical foundations of DBS including basal ganglia pathophysiological models, classic principles electrical stimulation, technical components system, risks, future directions DBS. Chronic high frequency induces number functional changes from fast physiological to slower metabolic effects ultimately leads structural reorganization brain, so-called neuroplasticity. Examples each these fast, slow, long-term are given in context where mechanisms have perhaps been most intensely investigated. In particular, details striatal dopamine release, expression trophic factors, possible neuroprotective mechanism highlighted. We close with brief discussion clinical considerations improvement. will continue offer reversible safe therapeutic host neurological conditions remains one best windows into human physiology.

Language: Английский

Citations

134
Compression of Cerebellar Functional Gradients in Schizophrenia DOI Open Access
Debo Dong, Cheng Luo, Xavier Guell

et al.

Schizophrenia Bulletin, Journal Year: 2020, Volume and Issue: 46(5), P. 1282 - 1295

Published: Feb. 1, 2020

Abstract Our understanding of cerebellar involvement in brain disorders has evolved from motor processing to high-level cognitive and affective processing. Recent neuroscience progress highlighted hierarchy as a fundamental principle for the organization. Despite substantial research on dysfunction schizophrenia, there is need establish neurobiological framework better understand co-occurrence interaction low- functional abnormalities cerebellum schizophrenia. To help such framework, we investigated distribution sensorimotor-supramodal hierarchical topography cerebellar-cerebral circuits schizophrenia using novel gradient-based resting-state connectivity (FC) analysis (96 patients with vs 120 healthy controls). We found showed compression principal motor-to-supramodal gradient. Specifically, were increased gradient values sensorimotor regions decreased supramodal regions, resulting shorter distance (compression) between poles this This pattern was observed intra-cerebellar, cerebellar-cerebral, cerebral-cerebellar FC. Further investigation revealed hyper-connectivity cognition areas within cerebellum, cerebral areas, possibly contributing compressed pattern. These findings present mechanism that may underlie cerebro-cerebellar Within abnormal organization, cascade impairments stemming disrupted low-level system part account

Language: Английский

Citations

92
Neural Correlates of Reinforcement Learning in Mid-lateral Cerebellum DOI Creative Commons
Naveen Sendhilnathan, Mulugeta Semework, Michael E. Goldberg

et al.

Neuron, Journal Year: 2020, Volume and Issue: 106(1), P. 188 - 198.e5

Published: Jan. 27, 2020

Language: Английский

Citations

87
Brain ethanol metabolism by astrocytic ALDH2 drives the behavioural effects of ethanol intoxication DOI
Shiyun Jin, Qi Cao, Fanghan Yang

et al.

Nature Metabolism, Journal Year: 2021, Volume and Issue: 3(3), P. 337 - 351

Published: March 22, 2021

Language: Английский

Citations

87
Abnormal Cerebellar Development in Autism Spectrum Disorders DOI Open Access
Meike E. van der Heijden, Jason S. Gill, Roy V. Sillitoe

et al.

Developmental Neuroscience, Journal Year: 2021, Volume and Issue: 43(3-4), P. 181 - 190

Published: Jan. 1, 2021

Autism spectrum disorders (ASD) comprise a group of heterogeneous neurodevelopmental conditions characterized by impaired social interactions and repetitive behaviors with symptom onset in early infancy. The genetic risks for ASD have long been appreciated: concordance diagnosis may be as high 90% monozygotic twins 30% dizygotic twins, hundreds mutations single genes associated ASD. Nevertheless, only 5–30% cases can explained known cause, suggesting that genetics is not the factor at play. More recently, several studies reported up to 40% infants cerebellar hemorrhages lesions are diagnosed These overrepresented severely premature infants, who born during period highly dynamic development encompasses an approximately 5-fold size expansion, increase structural complexity, remarkable rearrangements local neural circuits. incidence ASD-causing this window supports hypothesis abnormal primary risk However, links between developmental deficits cerebellum neurological dysfunctions underlying completely understood. Here, we discuss key processes development, what happens circuit when interrupted, how function leads cognitive impairments. We explore central question: Is important generation brain or part itself?

Language: Английский

Citations

73