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The Neuroscientist : a Review Journal... Jun 2019Fundamental for understanding cerebellar function is determining the representations in Purkinje cell activity, the sole output of the cerebellar cortex. Up to the... (Review)
Review
Fundamental for understanding cerebellar function is determining the representations in Purkinje cell activity, the sole output of the cerebellar cortex. Up to the present, the most accurate descriptions of the information encoded by Purkinje cells were obtained in the context of motor behavior and reveal a high degree of heterogeneity of kinematic and performance error signals encoded. The most productive framework for organizing Purkinje cell firing representations is provided by the forward internal model hypothesis. Direct tests of this hypothesis show that individual Purkinje cells encode two different forward models simultaneously, one for effector kinematics and one for task performance. Newer results demonstrate that the timing of simple spike encoding of motor parameters spans an extend interval of up to ±2 seconds. Furthermore, complex spike discharge is not limited to signaling errors, can be predictive, and dynamically controls the information in the simple spike firing to meet the demands of upcoming behavior. These rich, diverse, and changing representations highlight the integrative aspects of cerebellar function and offer the opportunity to generalize the cerebellar computational framework over both motor and non-motor domains.
Topics: Action Potentials; Animals; Biomechanical Phenomena; Feedback, Physiological; Humans; Models, Neurological; Movement; Psychomotor Performance; Purkinje Cells
PubMed: 29985093
DOI: 10.1177/1073858418785628 -
Brain Research Bulletin Mar 2017Since the groundbreaking work of Ramon y Cajal, the cerebellar Purkinje cell has always represented an ideal model for studying the organization, development and... (Review)
Review
Since the groundbreaking work of Ramon y Cajal, the cerebellar Purkinje cell has always represented an ideal model for studying the organization, development and function of synaptic circuits. Purkinje cells receive distinct types of glutamatergic and GABAergic synapses, each characterized by exquisite sub-cellular and molecular specificity. The formation and refinement of these connections results from a temporally-regulated sequence of events that involves molecular interactions between distinct sets of secreted and surface proteins, as well as activity-dependent competition between converging inputs. Insights into the mechanisms controlling synaptic specificity in Purkinje cells may help understand synapse development also in other brain regions and disclose circuit abnormalities that underlie neurodevelopmental disorders.
Topics: Animals; Humans; Models, Neurological; Purkinje Cells; Synapses
PubMed: 27721030
DOI: 10.1016/j.brainresbull.2016.10.004 -
Nature Communications Jul 2023The classification of neuronal subpopulations has significantly advanced, yet its relevance for behavior remains unclear. The highly organized flocculus of the...
The classification of neuronal subpopulations has significantly advanced, yet its relevance for behavior remains unclear. The highly organized flocculus of the cerebellum, known to fine-tune multi-axial eye movements, is an ideal substrate for the study of potential functions of neuronal subpopulations. Here, we demonstrate that its recently identified subpopulations of 9+ and 9- Purkinje cells exhibit an intermediate Aldolase C expression and electrophysiological profile, providing evidence for a graded continuum of intrinsic properties among PC subpopulations. By identifying and utilizing two Cre-lines that genetically target these floccular domains, we show with high spatial specificity that these subpopulations of Purkinje cells participate in separate micromodules with topographically organized connections. Finally, optogenetic excitation of the respective subpopulations results in movements around the same axis in space, yet with distinct kinematic profiles. These results indicate that Purkinje cell subpopulations integrate in discrete circuits and mediate particular parameters of single movements.
Topics: Purkinje Cells; Biomechanical Phenomena; Eye Movements; Cerebellum; Movement
PubMed: 37468512
DOI: 10.1038/s41467-023-40111-5 -
Journal of Molecular and Cellular... Nov 2008Cardiac Purkinje fibers, due to their unique anatomical location, cell structure and electrophysiologic characteristics, play an important role in cardiac conduction and... (Review)
Review
Cardiac Purkinje fibers, due to their unique anatomical location, cell structure and electrophysiologic characteristics, play an important role in cardiac conduction and arrhythmogenesis. Purkinje cell action potentials are longer than their ventricular counterpart, and display two levels of resting potential. Purkinje cells provide for rapid propagation of the cardiac impulse to ventricular cells and have pacemaker and triggered activity, which differs from ventricular cells. Additionally, a unique intracellular Ca2+ release coordination has been revealed recently for the normal Purkinje cell. However, since the isolation of single Purkinje cells is difficult, particularly in small animals, research using Purkinje cells has been restricted. This review concentrates on comparison of Purkinje and ventricular cells in the morphology of the action potential, ionic channel function and molecular determinants by summarizing our present day knowledge of Purkinje cells.
Topics: Action Potentials; Animals; Calcium; Connexins; Female; Heart Ventricles; Humans; Ion Channels; Ions; Male; Models, Biological; Potassium; Protein Isoforms; Purkinje Cells; Sodium
PubMed: 18778712
DOI: 10.1016/j.yjmcc.2008.08.001 -
Cerebellum (London, England) Aug 2016Several lines of evidence show that classical or Pavlovian conditioning of blink responses depends on the cerebellum. Recordings from cerebellar Purkinje cells that... (Review)
Review
Several lines of evidence show that classical or Pavlovian conditioning of blink responses depends on the cerebellum. Recordings from cerebellar Purkinje cells that control the eyelid and the conditioned blink show that during training with a conditioning protocol, a Purkinje cell develops a pause response to the conditional stimulus. This conditioned cellular response has many of the properties that characterise the overt blink. The present paper argues that the learned Purkinje cell pause response is the memory trace and main driver of the overt conditioned blink and that it explains many well-known behavioural phenomena.
Topics: Animals; Blinking; Conditioning, Classical; Conditioning, Eyelid; Memory; Purkinje Cells
PubMed: 26400585
DOI: 10.1007/s12311-015-0722-4 -
Progress in Neurobiology Aug 2003The object of this review is to assemble much of the literature concerning Purkinje cell death in cerebellar pathology and to relate this to what is now known about the... (Review)
Review
The object of this review is to assemble much of the literature concerning Purkinje cell death in cerebellar pathology and to relate this to what is now known about the complex topography of the cerebellar cortex. A brief introduction to Purkinje cells, and their regionalization is provided, and then the data on Purkinje cell death in mouse models and, where appropriate, their human counterparts, have been arranged according to several broad categories--naturally-occurring and targeted mutations leading to Purkinje cell death, Purkinje cell death due to toxins, Purkinje cell death in ischemia, Purkinje cell death in infection and in inherited disorders, etc. The data reveal that cerebellar Purkinje cell death is much more topographically complex than is usually appreciated.
Topics: Animals; Cell Death; Cerebellar Cortex; Cerebellum; Disease Models, Animal; Humans; Mice; Mutation; Neurotoxins; Purkinje Cells; Receptors, Glutamate
PubMed: 14568361
DOI: 10.1016/s0301-0082(03)00114-x -
Journal of Visualized Experiments : JoVE Dec 2019Organotypic slice culture is a powerful in vitro model that mimicks in vivo conditions more closely than dissociated primary cell cultures. In early postnatal...
Organotypic slice culture is a powerful in vitro model that mimicks in vivo conditions more closely than dissociated primary cell cultures. In early postnatal development, cerebellar Purkinje cells are known to go through a vulnerable period, during which they undergo programmed cell death. Here, we provide a detailed protocol to perform mouse organotypic cerebellar slice culture during this critical time. The slices are further labeled to assess Purkinje cell survival and the efficacy of neuroprotective treatments. This method can be extremely valuable to screen for new neuroactive molecules.
Topics: Animals; Cell Survival; Mice; Organ Culture Techniques; Purkinje Cells
PubMed: 31904025
DOI: 10.3791/60353 -
ELife Sep 2020Ramón y Cajal proclaimed the neuron doctrine based on circuit features he exemplified using cerebellar basket cell projections. Basket cells form dense inhibitory...
Ramón y Cajal proclaimed the neuron doctrine based on circuit features he exemplified using cerebellar basket cell projections. Basket cells form dense inhibitory plexuses that wrap Purkinje cell somata and terminate as pinceaux at the initial segment of axons. Here, we demonstrate that HCN1, Kv1.1, PSD95 and GAD67 unexpectedly mark patterns of basket cell pinceaux that map onto Purkinje cell functional zones. Using cell-specific genetic tracing with an mouse conditional allele, we reveal that basket cell zones comprise different sizes of pinceaux. We tested whether Purkinje cells instruct the assembly of inhibitory projections into zones, as they do for excitatory afferents. Genetically silencing Purkinje cell neurotransmission blocks the formation of sharp Purkinje cell zones and disrupts excitatory axon patterning. The distribution of pinceaux into size-specific zones is eliminated without Purkinje cell GABAergic output. Our data uncover the cellular and molecular diversity of a foundational synapse that revolutionized neuroscience.
Topics: Animals; Female; Male; Mice; Purkinje Cells; Synaptic Transmission
PubMed: 32990595
DOI: 10.7554/eLife.55569 -
Cerebellum (London, England) Dec 2018Cerebellar Purkinje neurons are arguably some of the most conspicuous neurons in the vertebrate central nervous system. They have characteristic planar fan-shaped...
Cerebellar Purkinje neurons are arguably some of the most conspicuous neurons in the vertebrate central nervous system. They have characteristic planar fan-shaped dendrites which branch extensively and fill spaces almost completely with little overlap. This dendritic morphology is well suited to receiving a single or a few excitatory synaptic inputs from each of more than 100,000 parallel fibers which run orthogonally to Purkinje cell dendritic trees. In contrast, another type of excitatory input to a Purkinje neuron is provided by a single climbing fiber, which forms some hundreds to thousands of synapses with a Purkinje neuron. This striking contrast between the two types of synaptic inputs to a Purkinje neuron has attracted many neuroscientists. It is also to be noted that Purkinje neurons are the sole neurons sending outputs from the cerebellar cortex. In other words, all computational results within the cortex are transmitted by Purkinje cell axons, which inhibit neurons in the cerebellar or vestibular nucleus. Notably, Purkinje neurons show several forms of synaptic plasticity. Among them, long-term depression (LTD) at parallel fiber synapses has been regarded as a putatively essential mechanism for cerebellum-dependent learning. In this special issue on Purkinje neurons, you will find informative reviews and original papers on the development, characteristics and functions of Purkinje neurons, or related themes contributed by outstanding researchers.
Topics: Animals; Cerebellum; Humans; Purkinje Cells
PubMed: 30284678
DOI: 10.1007/s12311-018-0985-7 -
Life Science Alliance Sep 2023Niemann-Pick disease type C1 (NPC1) is a fatal lysosomal storage disorder characterized by progressive neuronal degeneration. Its key pathogenic events remain largely...
Niemann-Pick disease type C1 (NPC1) is a fatal lysosomal storage disorder characterized by progressive neuronal degeneration. Its key pathogenic events remain largely unknown. We have, herein, found that neonatal BM-derived cell transplantation can ameliorate Purkinje cell degeneration in NPC1 mice. We subsequently addressed the impact of the peripheral immune system on the neuropathogenesis observed in NPC1 mice. The depletion of mature lymphocytes promoted NPC1 phenotypes, thereby suggesting a neuroprotective effect of lymphocytes. Moreover, the peripheral infusion of CD4-positive cells (specifically, of regulatory T cells) from normal healthy donor ameliorated the cerebellar ataxic phenotype and enhanced the survival of Purkinje cells. Conversely, the depletion of regulatory T cells enhanced the onset of the neurological phenotype. On the other hand, circulating inflammatory monocytes were found to be involved in the progression of Purkinje cell degeneration, whereas the depletion of resident microglia had little effect. Our findings reveal a novel role of the adaptive and the innate immune systems in NPC1 neuropathology.
Topics: Mice; Animals; Purkinje Cells; Niemann-Pick Disease, Type C; Cerebellum; Immune System; Microglia
PubMed: 37369603
DOI: 10.26508/lsa.202201881