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Proceedings of the National Academy of... Apr 2022
Topics: Cerebellum; Purkinje Cells
PubMed: 35452313
DOI: 10.1073/pnas.2204155119 -
Neuroscience May 2021This article is dedicated to the memory of Masao Ito. Masao Ito made numerous important contributions revealing the function of the cerebellum in motor control. His... (Review)
Review
This article is dedicated to the memory of Masao Ito. Masao Ito made numerous important contributions revealing the function of the cerebellum in motor control. His pioneering contributions to cerebellar physiology began with his discovery of inhibition and disinhibition of target neurons by cerebellar Purkinje cells, and his discovery of the presence of long-term depression in parallel fiber-Purkinje cell synapses. Purkinje cells formed the nodal point of Masao Ito's landmark model of motor control by the cerebellum. These discoveries became the basis for his ideas regarding the flocculus hypothesis, the adaptive motor control system, and motor learning by the cerebellum, inspiring many new experiments to test his hypotheses. This article will trace the achievements of Ito and colleagues in analyzing the neural circuits of the input-output organization of the cerebellar cortex and nuclei, particularly with respect to motor control. The article will discuss some of the important issues that have been solved and also those that remain to be solved for our understanding of motor control by the cerebellum.
Topics: Cell Nucleus; Cerebellar Nuclei; Cerebellar Vermis; Cerebellum; Memory; Purkinje Cells
PubMed: 32768619
DOI: 10.1016/j.neuroscience.2020.07.051 -
Acta Neurologica Belgica Oct 2023
Topics: Infant, Newborn; Humans; Cerebellum; Hydrocephalus; Cerebellar Diseases; Infant, Newborn, Diseases; Rhombencephalon; Magnetic Resonance Imaging
PubMed: 36064837
DOI: 10.1007/s13760-022-02080-2 -
Diabetes Sep 2021The dorsal vagal complex (DVC) in the hindbrain, composed of the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus, plays a critical... (Review)
Review
The dorsal vagal complex (DVC) in the hindbrain, composed of the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus, plays a critical role in modulating satiety. The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) act directly in the brain to modulate feeding, and receptors for both are expressed in the DVC. Given the impressive clinical responses to pharmacologic manipulation of incretin signaling, understanding the central mechanisms by which incretins alter metabolism and energy balance is of critical importance. Here, we review recent single-cell approaches used to detect molecular signatures of GLP-1 and GIP receptor-expressing cells in the DVC. In addition, we discuss how current advancements in single-cell transcriptomics, epigenetics, spatial transcriptomics, and circuit mapping techniques have the potential to further characterize incretin receptor circuits in the hindbrain.
Topics: Animals; Feeding Behavior; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Receptors, Gastrointestinal Hormone; Rhombencephalon; Single-Cell Analysis
PubMed: 34176785
DOI: 10.2337/dbi21-0003 -
Cell Reports May 2023Within the cerebellar cortex, mossy fibers (MFs) excite granule cells (GCs) that excite Purkinje cells (PCs), which provide outputs to the deep cerebellar nuclei (DCNs)....
Within the cerebellar cortex, mossy fibers (MFs) excite granule cells (GCs) that excite Purkinje cells (PCs), which provide outputs to the deep cerebellar nuclei (DCNs). It is well established that PC disruption produces motor deficits such as ataxia. This could arise from either decreases in ongoing PC-DCN inhibition, increases in the variability of PC firing, or disruption of the flow of MF-evoked signals. Remarkably, it is not known whether GCs are essential for normal motor function. Here we address this issue by selectively eliminating calcium channels that mediate transmission (Ca2.1, Ca2.2, and Ca2.3) in a combinatorial manner. We observe profound motor deficits but only when all Ca2 channels are eliminated. In these mice, the baseline rate and variability of PC firing are unaltered, and locomotion-dependent increases in PC firing are eliminated. We conclude that GCs are indispensable for normal motor performance and that disruption of MF-induced signals impairs motor performance.
Topics: Mice; Animals; Cerebellum; Neurons; Purkinje Cells; Cerebellar Cortex; Signal Transduction
PubMed: 37141091
DOI: 10.1016/j.celrep.2023.112429 -
Neuroscience May 2021Fifty years have passed since David Marr, Masao Ito, and James Albus proposed seminal models of cerebellar functions. These models share the essential concept that... (Review)
Review
Fifty years have passed since David Marr, Masao Ito, and James Albus proposed seminal models of cerebellar functions. These models share the essential concept that parallel-fiber-Purkinje-cell synapses undergo plastic changes, guided by climbing-fiber activities during sensorimotor learning. However, they differ in several important respects, including holistic versus complementary roles of the cerebellum, pattern recognition versus control as computational objectives, potentiation versus depression of synaptic plasticity, teaching signals versus error signals transmitted by climbing-fibers, sparse expansion coding by granule cells, and cerebellar internal models. In this review, we evaluate different features of the three models based on recent computational and experimental studies. While acknowledging that the three models have greatly advanced our understanding of cerebellar control mechanisms in eye movements and classical conditioning, we propose a new direction for computational frameworks of the cerebellum, that is, hierarchical reinforcement learning with multiple internal models.
Topics: Cerebellum; Models, Neurological; Neuronal Plasticity; Purkinje Cells; Synapses
PubMed: 32599123
DOI: 10.1016/j.neuroscience.2020.06.019 -
Nature Reviews. Neuroscience Nov 2020
Topics: Drinking; Feedback; Humans; Hunger; Rhombencephalon; Taste; Thirst
PubMed: 32913320
DOI: 10.1038/s41583-020-00380-1 -
ELife Aug 2020High-end technical approaches help to untangle the substructure and projection patterns of the cerebellum.
High-end technical approaches help to untangle the substructure and projection patterns of the cerebellum.
Topics: Cerebellum
PubMed: 32812869
DOI: 10.7554/eLife.60852 -
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 -
ENeuro 2021Feeding and breathing are two functions vital to the survival of all vertebrate species. Throughout the evolution, vertebrates living in different environments have... (Review)
Review
Feeding and breathing are two functions vital to the survival of all vertebrate species. Throughout the evolution, vertebrates living in different environments have evolved drastically different modes of feeding and breathing through using diversified orofacial and pharyngeal (oropharyngeal) muscles. The oropharyngeal structures are controlled by hindbrain neural circuits. The developing hindbrain shares strikingly conserved organizations and gene expression patterns across vertebrates, thus begs the question of how a highly conserved hindbrain generates circuits subserving diverse feeding/breathing patterns. In this review, we summarize major modes of feeding and breathing and principles underlying their coordination in many vertebrate species. We provide a hypothesis for the existence of a common hindbrain circuit at the phylotypic embryonic stage controlling oropharyngeal movements that is shared across vertebrate species; and reconfiguration and repurposing of this conserved circuit give rise to more complex behaviors in adult higher vertebrates.
Topics: Animals; Biological Evolution; Rhombencephalon; Vertebrates
PubMed: 33707205
DOI: 10.1523/ENEURO.0435-20.2021