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Cerebellum (London, England) Dec 2018The climbing fiber-Purkinje cell circuit is one of the most powerful and highly conserved in the central nervous system. Climbing fibers exert a powerful excitatory... (Review)
Review
The climbing fiber-Purkinje cell circuit is one of the most powerful and highly conserved in the central nervous system. Climbing fibers exert a powerful excitatory action that results in a complex spike in Purkinje cells and normal functioning of the cerebellum depends on the integrity of climbing fiber-Purkinje cell synapse. Over the last 50 years, multiple hypotheses have been put forward on the role of the climbing fibers and complex spikes in cerebellar information processing and motor control. Central to these theories is the nature of the interaction between the low-frequency complex spike discharge and the high-frequency simple spike firing of Purkinje cells. This review examines the major hypotheses surrounding the action of the climbing fiber-Purkinje cell projection, discussing both supporting and conflicting findings. The review describes newer findings establishing that climbing fibers and complex spikes provide predictive signals about movement parameters and that climbing fiber input controls the encoding of behavioral information in the simple spike firing of Purkinje cells. Finally, we propose the dynamic encoding hypothesis for complex spike function that strives to integrate established and newer findings.
Topics: Action Potentials; Animals; Models, Neurological; Motor Activity; Olivary Nucleus; Purkinje Cells
PubMed: 29982917
DOI: 10.1007/s12311-018-0960-3 -
Cerebellum (London, England) Sep 2009Physiological cell death is crucial for matching defined cellular populations within the central nervous system. Whereas the time course of developmental cell death in...
Physiological cell death is crucial for matching defined cellular populations within the central nervous system. Whereas the time course of developmental cell death in the central nervous system is well analyzed, information about its precise spatial patterning is scarce. Yet, the latter one is needed to appraise its contribution to circuit formation and refinement. Here, we document that during normal cerebellar development, dying Purkinje cells were highly localized within the vermal midline and in a lobule specific, parasagittal pattern along the whole mediolateral axis. In addition, single hot spots of cell death localized to the caudal declive and ventral lobule IX within the posterolateral fissure. These hot spots of dying Purkinje cells partly overlapped with gaps within the Purkinje cell layer which supports the classification of different gaps based on histological and molecular criteria, i.e., midline gap, patchy gaps, and raphes. Areas characterized by a high incidence of Purkinje cell death and gaps colocalize with known molecular and functional boundaries within the cerebellar cortex. Physiological cell death can thus be considered to serve as an important regulator of cerebellar histogenesis.
Topics: Animals; Animals, Newborn; Cell Death; Cell Movement; Cerebellum; Gene Expression Regulation, Developmental; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Nerve Tissue Proteins; Purkinje Cells; Time Factors
PubMed: 19238501
DOI: 10.1007/s12311-009-0093-9 -
Histology and Histopathology Jul 2001Some neurons, including cerebellar Purkinje cells, are completely ensheathed by astrocytes. When granule cell neurons and functional glia were eliminated from newborn... (Review)
Review
Some neurons, including cerebellar Purkinje cells, are completely ensheathed by astrocytes. When granule cell neurons and functional glia were eliminated from newborn mouse cerebellar cultures by initial exposure to a DNA synthesis inhibitor, Purkinje cells lacked glial sheaths and there was a tremendous sprouting of Purkinje cell recurrent axon collaterals, terminals of which hyperinnervated Purkinje cell somata, including persistent somatic spines, and formed heterotypical synapses with Purkinje cell dendritic spines, sites usually occupied by parallel fiber (granule cell axon) terminals. Purkinje cells in such preparations failed to develop complex spikes when recorded from intracellularly, and their membrane input resistances were low, making them less sensitive to inhibitory input. If granule cells and oligodendrocytes were eliminated, but astrocytes were not compromised, sprouting of recurrent axon collaterals occurred and their terminals projected to Purkinje cell dendritic spines, but the Purkinje cells had astrocytic sheaths, their somata were not hyperinnervated, the somatic spines had disappeared, complex spike discharges predominated, and membrane input resistance was like that of Purkinje cells in untreated control cultures. When cerebellar cultures without granule cells and glia were transplanted with granule cells and/or glia from another source, a series of changes occurred that included stripping of excess Purkinje cell axosomatic synapses by astrocytic processes, reduction of heterotypical axospinous synapses in the presence of astrocytes, disappearance of Purkinje cell somatic spines with astrocytic ensheathment, and proliferation of Purkinje cell dendritic spines after the introduction of astrocytes. Dendritic spine proliferation was followed by formation of homotypical axospinous synapses when granule cells were present or persistence as unattached spines in the absence of granule cells. The results of these studies indicate that astrocytes regulate the numbers of Purkinje cell axosomatic and axospinous synapses, induce Purkinje cell dendritic spine proliferation, and promote the structural and functional maturation of Purkinje cells.
Topics: Animals; Astrocytes; Axons; Cell Communication; Cell Differentiation; Cells, Cultured; Dendrites; Electrophysiology; Mice; Microscopy, Electron; Purkinje Cells; Synapses
PubMed: 11510987
DOI: 10.14670/HH-16.955 -
Cerebellum (London, England) Dec 2018Cerebellar Purkinje cells arborize unique dendrites that exhibit a planar, fan shape. The dendritic branches fill the space of their receptive field with little overlap.... (Review)
Review
Cerebellar Purkinje cells arborize unique dendrites that exhibit a planar, fan shape. The dendritic branches fill the space of their receptive field with little overlap. This dendritic arrangement is well-suited to form numerous synapses with the afferent parallel fibers of the cerebellar granule cells in a non-redundant manner. Purkinje cell dendritic arbor morphology is achieved by a combination of dynamic local branch growth behaviors, including elongation, branching, and retraction. Impacting these behaviors, the self-avoidance of each branch terminal is essential to form the non-overlapping dendritic configuration. This review outlines recent advances in our understanding of the cellular and molecular mechanisms of dendrite formation during cerebellar Purkinje cell development.
Topics: Animals; Cerebellum; Dendrites; Neuronal Outgrowth; Purkinje Cells
PubMed: 30270408
DOI: 10.1007/s12311-018-0984-8 -
The Journal of Comparative Neurology Jan 1989We have used the immunohistochemical detection of the Purkinje cell marker cGMP-dependent protein kinase to identify Purkinje neurons in the cerebellum of the reeler...
We have used the immunohistochemical detection of the Purkinje cell marker cGMP-dependent protein kinase to identify Purkinje neurons in the cerebellum of the reeler mutant mouse. Our quantitative analysis of Purkinje cell number based on this marker indicates that reeler mice possess approximately 82,000 Purkinje cells, slightly less than half the number found in normal mice. Our analysis also shows that 5% of the Purkinje cells in reeler are located in a normal position (between molecular and granular layers), 10% are found in the granular layer, and the remainder form the deep cellular masses characteristic of the reeler cerebellum. The finding of a major Purkinje cell deficit in reeler was surprising in that most investigators consider this mutation to effect cell migration as opposed to cell number. Although we cannot determine whether the Purkinje cell loss in reeler is a primary or secondary gene effect, the possibility that the reeler gene has its effect on migration through a primary effect on neurogenesis or cell survival should be considered.
Topics: Animals; Cell Count; Immunohistochemistry; Mice; Mice, Neurologic Mutants; Protein Kinases; Purkinje Cells
PubMed: 2918086
DOI: 10.1002/cne.902790404 -
Neuroscience Jan 1984Purkinje cell maturation during thyroxine-induced metamorphosis in premetamorphic bullfrog tadpoles was studied using electron microscopy and Golgi (silver-impregnated)...
Purkinje cell maturation during thyroxine-induced metamorphosis in premetamorphic bullfrog tadpoles was studied using electron microscopy and Golgi (silver-impregnated) preparations. Cerebella from tadpoles were examined following 1, 2, or 3 weeks of thyroxine treatment. Particular attention was paid to possible differences between the two populations of Purkinje cells previously described, i.e. (i) the smaller population located in the dorsal part of the cerebellum, where the Purkinje cells show dendritic arborization long before the appearance of the external granular layer, and (ii) the larger population located in the middle and ventral regions of the cerebellum, where the Purkinje cells begin to undergo maturation during metamorphosis when the external granular layer is established. Following thyroxine treatment, both populations of Purkinje cells showed rapid maturational change. In the mature (dorsal) group, dendritic growth resumed in the presence of an external granular layer increasing the complexity of their dendritic arbors. Moreover, climbing fiber synapses translocated from contacts on the soma to the thorns of growing dendrites, and somatic processes often disappeared. The immature (ventral) group showed dramatic differentiation of the perikaryon including polarization of cytoplasm with subsequent dendritic outgrowth and formation of somatic processes in the presence of climbing fibers. Stellate cell contacts appeared on the smooth portion of the soma of many Purkinje cells. Dendritic growth during thyroxine-induced metamorphosis was characterized by growth (elongation) with minimal branching, which is initially observed during spontaneous metamorphosis. Typically, these growing dendrites ended in growth cones, some with one or several filopodia. Developing Purkinje cell dendritic spines formed synapses with parallel fibers. The present study has provided an example of the dramatic nature of thyroxine's action in inducing the complex series of detailed maturational changes in the cerebellum 1-2 yr ahead of schedule. In addition, the results show that thyroxine-induced Purkinje cell maturation is more rapid and synchronous than that seen during spontaneous metamorphosis. It is concluded that Purkinje cell maturation during metamorphosis is largely dependent on thyroid hormone.
Topics: Animals; Cell Differentiation; Dendrites; Metamorphosis, Biological; Microscopy, Electron; Purkinje Cells; Rana catesbeiana; Synapses; Thyroxine
PubMed: 6608700
DOI: 10.1016/0306-4522(84)90219-7 -
Movement Disorders : Official Journal... Nov 2013Although essential tremor (ET) is among the most prevalent neurological diseases, its precise pathogenesis is not understood. Purkinje cell loss has been observed in...
Although essential tremor (ET) is among the most prevalent neurological diseases, its precise pathogenesis is not understood. Purkinje cell loss has been observed in some studies and is the focus of interest and debate. Expressing these data as Purkinje cells/layer length allows one to adjust for the inherent curved nature of the cerebellar folia. Capitalizing on the Essential Tremor Centralized Brain Repository, we quantified Purkinje cell linear density in cases versus controls. Free-floating 100-μm parasagittal cerebellar hemispheric sections were subjected to rabbit polyclonal anti-Calbindin D28k antibody, and 10 random fields/brain were selected for quantification of Purkinje cells/mm(-1) Purkinje cell layer. Purkinje cell linear density was lower in 32 ET cases than in16 controls (1.14 ± 0.32 vs. 1.35 ± 0.31/mm(-1) , P = 0.03). Purkinje cell linear density was inversely associated with torpedo count (r = -0.38, P = 0.028). The current sample of ET cases demonstrates a reduction in Purkinje cell number relative to that of controls. Greater Purkinje cell axonal remodeling (torpedoes) was found in individuals who had the most Purkinje cell drop out. The role of Purkinje cell loss in the pathogenesis of this disorder merits additional study.
Topics: Aged; Aged, 80 and over; Calbindin 1; Cell Count; Cerebellum; Essential Tremor; Female; Functional Laterality; Humans; Male; Purkinje Cells; Statistics, Nonparametric
PubMed: 23925732
DOI: 10.1002/mds.25629 -
Cell Reports Mar 2020The functional impact of single interneurons on neuronal output in vivo and how interneurons are recruited by physiological activity patterns remain poorly understood....
The functional impact of single interneurons on neuronal output in vivo and how interneurons are recruited by physiological activity patterns remain poorly understood. In the cerebellar cortex, molecular layer interneurons and their targets, Purkinje cells, receive excitatory inputs from granule cells and climbing fibers. Using dual patch-clamp recordings from interneurons and Purkinje cells in vivo, we probe the spatiotemporal interactions between these circuit elements. We show that single interneuron spikes can potently inhibit Purkinje cell output, depending on interneuron location. Climbing fiber input activates many interneurons via glutamate spillover but results in inhibition of those interneurons that inhibit the same Purkinje cell receiving the climbing fiber input, forming a disinhibitory motif. These interneuron circuits are engaged during sensory processing, creating diverse pathway-specific response functions. These findings demonstrate how the powerful effect of single interneurons on Purkinje cell output can be sculpted by various interneuron circuit motifs to diversify cerebellar computations.
Topics: Action Potentials; Animals; Interneurons; Mice; Nerve Net; Neural Inhibition; Purkinje Cells; Sensation; Time Factors
PubMed: 32130904
DOI: 10.1016/j.celrep.2020.02.009 -
Cerebellum (London, England) 2003Peripheral steroid hormones act on brain tissues through intracellular receptor-mediated mechanisms to regulate several important brain neuronal functions. The brain is... (Review)
Review
Peripheral steroid hormones act on brain tissues through intracellular receptor-mediated mechanisms to regulate several important brain neuronal functions. The brain is therefore considered to be a target site of steroid hormones. In contrast to this classical concept, new findings over the past decade have established that the brain itself also synthesizes steroids de novo from cholesterol through mechanisms at least partly independent of peripheral steroidogenic glands. Such steroids synthesized de novo in the brain, as well as other areas of the nervous system, are called neurosteroids. To analyze neurosteroid actions in the brain, we need data on the specific synthesis in particular sites of the brain at particular times. Such information is crucial to developing hypotheses predicting the potential roles of particular neurosteroids in the developing and adult brains. Thus our studies for this exciting area of brain research have focused on the biosynthesis of neurosteroids in the identified neurosteroidogenic cells underlying important brain functions. We have demonstrated that the Purkinje cell, a typical cerebellar neuron, is a major site for neurosteroid formation in the brain. This is the first observation of neuronal neurosteroidogenesis in the brain. Subsequently genomic and nongenomic actions of neurosteroids have been suggested by a series of our studies using an excellent Purkinje cellular model. Here we summarize the advances made in our understanding of biosynthesis of neurosteroids in the cerebellar Purkinje cell.
Topics: Animals; Humans; Purkinje Cells; Steroids
PubMed: 14509571
DOI: 10.1080/14734220310016169 -
Acta Neuropathologica Communications May 2021Fluorescent staining of newly transcribed RNA via metabolic labelling with 5-ethynyluridine (EU) and click chemistry enables visualisation of changes in transcription,...
Fluorescent staining of newly transcribed RNA via metabolic labelling with 5-ethynyluridine (EU) and click chemistry enables visualisation of changes in transcription, such as in conditions of cellular stress. Here, we tested whether EU labelling can be used to examine transcription in vivo in mouse models of nervous system disorders. We show that injection of EU directly into the cerebellum results in reproducible labelling of newly transcribed RNA in cerebellar neurons and glia, with cell type-specific differences in relative labelling intensities, such as Purkinje cells exhibiting the highest levels. We also observed EU-labelling accumulating into cytoplasmic inclusions, indicating that EU, like other modified uridines, may introduce non-physiological properties in labelled RNAs. Additionally, we found that EU induces Purkinje cell degeneration nine days after EU injection, suggesting that EU incorporation not only results in abnormal RNA transcripts, but also eventually becomes neurotoxic in highly transcriptionally-active neurons. However, short post-injection intervals of EU labelling in both a Purkinje cell-specific DNA repair-deficient mouse model and a mouse model of spinocerebellar ataxia 1 revealed reduced transcription in Purkinje cells compared to controls. We combined EU labelling with immunohistology to correlate altered EU staining with pathological markers, such as genotoxic signalling factors. These data indicate that the EU-labelling method provided here can be used to identify changes in transcription in vivo in nervous system disease models.
Topics: Animals; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Nerve Degeneration; Neurodegenerative Diseases; Purkinje Cells; Staining and Labeling; Transcription, Genetic; Uridine
PubMed: 34020718
DOI: 10.1186/s40478-021-01200-y