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Advances in Experimental Medicine and... 2020The integrity of the cerebellum is exquisitely dependent on peroxisomal β-oxidation metabolism. Patients with peroxisomal β-oxidation defects commonly develop... (Review)
Review
The integrity of the cerebellum is exquisitely dependent on peroxisomal β-oxidation metabolism. Patients with peroxisomal β-oxidation defects commonly develop malformation, leukodystrophy, and/or atrophy of the cerebellum depending on the gene defect and on the severity of the mutation. By analyzing mouse models lacking the central peroxisomal β-oxidation enzyme, multifunctional protein-2 (MFP2), either globally or in selected cell types, insights into the pathomechanisms could be obtained. All mouse models developed ataxia, but the onset was earlier in global and neural-selective (Nestin) Mfp2 knockout mice as compared to Purkinje cell (PC)-selective Mfp2 knockouts.At the histological level, this was associated with developmental anomalies in global and Nestin-Mfp2 mice, including aberrant wiring of PCs by parallel and climbing fibers and altered electrical properties of PCs. In all mouse models, dystrophy of PC axons with swellings initiating in the deep cerebellar nuclei and evolving to the proximal axon, preceded death of PCs. These degenerative features are in part mediated by deficient peroxisomal β-oxidation within PCs but are accelerated when MFP2 is also absent from other neural cell types. The metabolic causes of the diverse cerebellar pathologies remain unknown.In conclusion, peroxisomal β-oxidation is required both for the development and for the maintenance of the cerebellum. This is mediated by PC autonomous and nonautonomous mechanisms.
Topics: Animals; Axons; Cerebellum; Humans; Oxidation-Reduction; Peroxisomes; Purkinje Cells
PubMed: 33417211
DOI: 10.1007/978-3-030-60204-8_9 -
Histochemistry and Cell Biology Jul 2018The enormous expansion the vertebrate nervous system goes through from its first anlage to its adult shape and organization goes along with extensive rearrangements of... (Review)
Review
The enormous expansion the vertebrate nervous system goes through from its first anlage to its adult shape and organization goes along with extensive rearrangements of its constituent cells and typical cellular migrations, often over long distances, and by convoluted pathways. Here, I try to summarize how the cells that form the cerebellum move and migrate during normal cerebellar histogenesis. The cerebellum is made up of a limited set of clearly distinguishable classes of cells, some of which are also readily accessible by genetic tools. Its structure and development have been the focus of studies dating back to at least Ramon y Cajal which have yielded fundamental insights into basic mechanisms of the development of the nervous. During cerebellar histogenesis, several distinct and well-discernable modes of migration may be recognized, some of which have been studied in considerable morphological and molecular detail. Still, often grace to the detail known, a wealth of open questions remains, and the cerebellar anlage remains a highly accessible and promising paradigm for those interested in nervous system development and cell migration in general. I also point out some of the issues that may warrant consideration when results from technically distinct studies are compared and integrated.
Topics: Animals; Cell Movement; Cerebellum; Humans
PubMed: 29744613
DOI: 10.1007/s00418-018-1677-6 -
Nature Neuroscience Feb 2024
Topics: Cerebellum; Organoids
PubMed: 38326430
DOI: 10.1038/s41593-024-01583-w -
Neuron Aug 2023Information transmission between neural populations could occur through either coordinated changes in firing rates or the precise transmission of spike timing. We...
Information transmission between neural populations could occur through either coordinated changes in firing rates or the precise transmission of spike timing. We investigate the code for information transmission from a part of the cerebellar cortex that is crucial for the accurate execution of a quantifiable motor behavior. Simultaneous recordings from Purkinje cell pairs in the cerebellum of rhesus macaques reveal how these cells coordinate their activity to drive smooth pursuit eye movements. Purkinje cells show millisecond-scale coordination of spikes (synchrony), but the level of synchrony is small and insufficient to impact the firing of downstream vestibular nucleus neurons. Analysis of previous metrics that purported to reveal Purkinje cell synchrony demonstrates that these metrics conflate changes in firing rate and neuron-neuron covariance. We conclude that the output of the cerebellar cortex uses primarily a rate rather than a synchrony code to drive the activity of downstream neurons and thus control motor behavior.
Topics: Animals; Macaca mulatta; Cerebellum; Purkinje Cells; Neurons; Pursuit, Smooth; Action Potentials
PubMed: 37536289
DOI: 10.1016/j.neuron.2023.07.002 -
Frontiers in Neural Circuits 2021Classically, the cerebellum has been thought to play a significant role in motor coordination. However, a growing body of evidence for novel neural connections between... (Review)
Review
Classically, the cerebellum has been thought to play a significant role in motor coordination. However, a growing body of evidence for novel neural connections between the cerebellum and various brain regions indicates that the cerebellum also contributes to other brain functions implicated in reward, language, and social behavior. Cerebellar Purkinje cells (PCs) make inhibitory GABAergic synapses with their target neurons: other PCs and Lugaro/globular cells via PC axon collaterals, and neurons in the deep cerebellar nuclei (DCN) via PC primary axons. PC-Lugaro/globular cell connections form a cerebellar cortical microcircuit, which is driven by serotonin and noradrenaline. PCs' primary outputs control not only firing but also synaptic plasticity of DCN neurons following the integration of excitatory and inhibitory inputs in the cerebellar cortex. Thus, strong PC-mediated inhibition is involved in cerebellar functions as a key regulator of cerebellar neural networks. In this review, we focus on physiological characteristics of GABAergic transmission from PCs. First, we introduce monoaminergic modulation of GABAergic transmission at synapses of PC-Lugaro/globular cell as well as PC-large glutamatergic DCN neuron, and a Lugaro/globular cell-incorporated microcircuit. Second, we review the physiological roles of perineuronal nets (PNNs), which are organized components of the extracellular matrix and enwrap the cell bodies and proximal processes, in GABA release from PCs to large glutamatergic DCN neurons and in cerebellar motor learning. Recent evidence suggests that alterations in PNN density in the DCN can regulate cerebellar functions.
Topics: Cerebellar Nuclei; Cerebellum; Extracellular Matrix; Neuronal Plasticity; Neurons; Purkinje Cells
PubMed: 34194302
DOI: 10.3389/fncir.2021.661899 -
Neuroimaging Clinics of North America Aug 2016This article presents an overview of published studies using conventional and quantitative MR imaging to describe normal development of the cerebellum prenatally and... (Review)
Review
This article presents an overview of published studies using conventional and quantitative MR imaging to describe normal development of the cerebellum prenatally and postnatally through 18 years of age. Normal cerebellar development and maturational processes are described here within the context of MR imaging morphology, microstructure, metabolism, and functional connectivity. In addition, strengths and weaknesses of these reviewed studies are critically appraised and new directions for future cerebellar MR imaging investigation are made.
Topics: Adolescent; Adolescent Development; Cerebellum; Child; Child Development; Child, Preschool; Evaluation Studies as Topic; Female; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Pregnancy
PubMed: 27423797
DOI: 10.1016/j.nic.2016.03.004 -
European Journal of Paediatric... Jul 2017Cerebellar size appears to be correlated with the long-term outcome of preterm infants. Two-dimensional cranial ultrasonography (2D-cUS) is the first-line, routine tool...
BACKGROUND
Cerebellar size appears to be correlated with the long-term outcome of preterm infants. Two-dimensional cranial ultrasonography (2D-cUS) is the first-line, routine tool to characterize newborn cerebral structures. Information regarding the accuracy of 2D-cUS for assessing cerebellar size is scarce.
OBJECTIVES
To assess the reliability of cerebellar size using 2D-cUS.
METHODS
Fifty infants were prospectively scanned for a variety of clinical indications. The scans were stored and then independently analyzed offline by two observers. The transverse cerebellar diameter coronally from the anterior and mastoid fontanels (TCD-AF and TCD-MF, respectively); the midsagittal cerebellar vermis height and the anterior-posterior diameter from the AF; and the width and height of the fourth ventricle coronally from the MF view were measured. Interobserver variability was assessed using the intraclass correlation (ICC) with 95% confidence interval (CI) for each of the paired measures.
RESULTS
A total 294 images were included in the analysis. The interobserver ICCs were TCD-AF = 0.85 (0.76-0.91), TCD-MF = 0.9 (0.83-0.94), vermis height = 0.79 (0.66-0.88), anterior-posterior vermis diameter = 0.71 (0.5-0.84), width of the fourth ventricle = 0.72 (0.33-0.9), height of the fourth ventricle = 0.86 (0.7-0.92). The ICC for the TCD comparing the AF and the MF approach was ≥0.9 for both observers.
CONCLUSIONS
The reliability of the offline 2D-cUS cerebellar size assessments is good, and TCD-MF is the most consistent measure. Further studies should address the predictive value for the neurodevelopmental outcome of serial cerebellar size assessments by 2D-cUS for preterm infants.
Topics: Cerebellum; Female; Humans; Infant, Newborn; Reproducibility of Results; Ultrasonography
PubMed: 28433244
DOI: 10.1016/j.ejpn.2017.03.010 -
NeuroImage. Clinical 2023To systematically investigate the topological organisation of morphological networks of the cerebellum using structural MRI and examine their clinical relevance in...
BACKGROUND
To systematically investigate the topological organisation of morphological networks of the cerebellum using structural MRI and examine their clinical relevance in chronic insomnia (CI).
METHODS
One hundred and one patients with CI and 102 healthy controls (HCs) were recruited in this study. Individual morphological networks of the cerebellum were constructed based on regional grey matter volume, and topologically characterised using weighted graph theory-based network approaches. Between-group comparisons were performed using permutation tests, and Spearman's correlation was used to examine the relationships between topological alterations and clinical variables.
RESULTS
Compared with HCs, patients with CI exhibited a lower normalised clustering coefficient. Locally, CI patients exhibited lower nodal efficiency in the cerebellar lobule VIIb and vermis regions, but higher nodal efficiency in the right cerebellar lobule VIIIa regions. No correlations were observed between network alterations and clinical variables.
CONCLUSIONS
Individual morphological network analysis provides a new strategy for investigating cerebellar morphometric changes in CI, and our findings may have important implications in establishing diagnostic and categorical biomarkers.
Topics: Humans; Connectome; Sleep Initiation and Maintenance Disorders; Cerebellum; Cerebellar Vermis; Cerebral Cortex
PubMed: 37603949
DOI: 10.1016/j.nicl.2023.103492 -
Neuroscience May 2021Molecular layer interneurons (MLIs) play an important role in cerebellar information processing by controlling Purkinje cell (PC) activity via inhibitory synaptic... (Review)
Review
Molecular layer interneurons (MLIs) play an important role in cerebellar information processing by controlling Purkinje cell (PC) activity via inhibitory synaptic transmission. A local MLI network, constructed from both chemical and electrical synapses, is organized into spatially structured clusters that amplify feedforward and lateral inhibition to shape the temporal and spatial patterns of PC activity. Several recent in vivo studies indicate that such MLI circuits contribute not only to sensorimotor information processing, but also to precise motor coordination and cognitive processes. Here, we review current understanding of the organization of MLI circuits and their roles in the function of the mammalian cerebellum.
Topics: Animals; Cerebellum; Electrical Synapses; Interneurons; Purkinje Cells; Synaptic Transmission
PubMed: 33075461
DOI: 10.1016/j.neuroscience.2020.10.008 -
Brain Research Jun 2016Women are more likely than men to suffer from post-traumatic stress disorder (PTSD) and major depression. In addition to their sex bias, these disorders share stress as... (Review)
Review
Women are more likely than men to suffer from post-traumatic stress disorder (PTSD) and major depression. In addition to their sex bias, these disorders share stress as an etiological factor and hyperarousal as a symptom. Thus, sex differences in brain arousal systems and their regulation by stress could help explain increased vulnerability to these disorders in women. Here we review preclinical studies that have identified sex differences in the locus coeruleus (LC)-norepinephrine (NE) arousal system. First, we detail how structural sex differences in the LC can bias females towards increased arousal in response to emotional events. Second, we highlight studies demonstrating that estrogen can increase NE in LC target regions by enhancing the capacity for NE synthesis, while reducing NE degradation, potentially increasing arousal in females. Third, we review data revealing how sex differences in the stress receptor, corticotropin releasing factor 1 (CRF1), can increase LC neuronal sensitivity to CRF in females compared to males. This effect could translate into hyperarousal in women under conditions of CRF hypersecretion that occur in PTSD and depression. The implications of these sex differences for the treatment of stress-related psychiatric disorders are discussed. Moreover, the value of using information regarding biological sex differences to aid in the development of novel pharmacotherapies to better treat men and women with PTSD and depression is also highlighted. This article is part of a Special Issue entitled SI: Noradrenergic System.
Topics: Animals; Humans; Locus Coeruleus; Sex Characteristics; Stress, Psychological
PubMed: 26607253
DOI: 10.1016/j.brainres.2015.11.021