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Progress in Brain Research 1988
Review
Topics: Animals; Cell Movement; Cerebellum; Dendrites; Mice; Mice, Neurologic Mutants; Nerve Degeneration; Neural Pathways; Purkinje Cells; Synapses
PubMed: 3073409
DOI: 10.1016/s0079-6123(08)60277-0 -
Differential Purkinje cell simple spike activity and pausing behavior related to cerebellar modules.Journal of Neurophysiology Apr 2015The massive computational capacity of the cerebellar cortex is conveyed by Purkinje cells onto cerebellar and vestibular nuclei neurons through their GABAergic,...
The massive computational capacity of the cerebellar cortex is conveyed by Purkinje cells onto cerebellar and vestibular nuclei neurons through their GABAergic, inhibitory output. This implies that pauses in Purkinje cell simple spike activity are potentially instrumental in cerebellar information processing, but their occurrence and extent are still heavily debated. The cerebellar cortex, although often treated as such, is not homogeneous. Cerebellar modules with distinct anatomical connectivity and gene expression have been described, and Purkinje cells in these modules also differ in firing rate of simple and complex spikes. In this study we systematically correlate, in awake mice, the pausing in simple spike activity of Purkinje cells recorded throughout the entire cerebellum, with their location in terms of lobule, transverse zone, and zebrin-identified cerebellar module. A subset of Purkinje cells displayed long (>500-ms) pauses, but we found that their occurrence correlated with tissue damage and lower temperature. In contrast to long pauses, short pauses (<500 ms) and the shape of the interspike interval (ISI) distributions can differ between Purkinje cells of different lobules and cerebellar modules. In fact, the ISI distributions can differ both between and within populations of Purkinje cells with the same zebrin identity, and these differences are at least in part caused by differential synaptic inputs. Our results suggest that long pauses are rare but that there are differences related to shorter intersimple spike intervals between and within specific subsets of Purkinje cells, indicating a potential further segregation in the activity of cerebellar Purkinje cells.
Topics: Action Potentials; Animals; Cerebellum; Male; Mice; Mice, Inbred C57BL; Purkinje Cells
PubMed: 25717166
DOI: 10.1152/jn.00925.2014 -
The Journal of Neuroscience : the... May 1997Purkinje cells are among the most resistant neurons to axotomy and the most refractory to axonal regeneration. By using organotypic cultures, we have studied age- and...
Purkinje cells are among the most resistant neurons to axotomy and the most refractory to axonal regeneration. By using organotypic cultures, we have studied age- and environment-related factors implicated in Purkinje cell survival and axonal regeneration. Most Purkinje cells taken from 1- to 5-d-old rats, the period in which these neurons are engaged in intense synaptogenesis and dendritic remodeling, die 1 week after plating, whereas if cultured before or after this period, Purkinje cells survive, even in the absence of deep nuclear neurons, their postsynaptic targets. Cerebellar slices taken from 10-d-old rats and kept in vitro for 1 week acquire a cellular composition resembling mature cerebellum. Their Purkinje cells are resistant to axotomy, but even when confronted with permissive environments (sciatic nerves or fetal cerebellar slices), their axons do not regenerate. In contrast, fetal rat and mouse Purkinje cells are able to regenerate their axons on mature cerebellar slices. This regeneration is massive, and the regrowing axons invade all cerebellar regions of the apposed mature slices, including white matter. These results show that Purkinje cell survival and axonal regeneration are age-related and independent from environmental constraints. Moreover, our observations suggest strongly that the onset of synaptogenesis of Purkinje cell axons could provide a signal to turn off their growth program and that, thereafter, permissive microenvironment alone is unable to reestablish such a program.
Topics: Animals; Axons; Calbindins; Cell Culture Techniques; Cell Survival; Cells, Cultured; Cellular Senescence; Cerebellar Nuclei; Denervation; Female; Mice; Mice, Knockout; Nerve Regeneration; Nerve Tissue Proteins; Pregnancy; Purkinje Cells; Rats; Rats, Wistar; S100 Calcium Binding Protein G; Sciatic Nerve
PubMed: 9133392
DOI: 10.1523/JNEUROSCI.17-10-03710.1997 -
Developmental Biology Mar 1996We utilized a strain of mice, derived from a radiation mutagenesis experiment and carrying an activity-attenuated allele of the X-linked enzyme glucose-6-phosphate...
We utilized a strain of mice, derived from a radiation mutagenesis experiment and carrying an activity-attenuated allele of the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD), to analyze the development of the cell lineage leading to cerebellar Purkinje neurons. Due to random X inactivation during early embryonic development, X- linked genes can be used to distinguish between clonally related populations of cells in X inactivation mosaics. Following histochemical staining for G6PD activity, the numeric proportions of Purkinje cells expressing either the wild-type or the mutant enzyme and the spatial distribution of these cellular phenotypes and their relation to anatomically and genetically defined cerebellar compartments were analyzed. Our data suggest that cerebellar Purkinje neurons originate from a limited pool of some 129 precursors. The size of this pool is different from the one derived from chimeric mice, allowing us to deduce the relative timing of Purkinje cell lineage restriction. Our data also show that Purkinje neurons of distinct lineage are extensively intermingled within the cerebellar cortex. Together, these findings suggest both a role for cell-cell communication in the development of genetically defined cerebellar compartments and a temporal window during which such cellular interactions may take place.
Topics: Animals; Cerebellar Cortex; Dosage Compensation, Genetic; Glucosephosphate Dehydrogenase; Heterozygote; Male; Mice; Mice, Inbred C3H; Mosaicism; Purkinje Cells
PubMed: 8631510
DOI: 10.1006/dbio.1996.0083 -
The Journal of Steroid Biochemistry and... Dec 2006New findings over the past decade have shown that the brain has the capability of forming steroids de novo from cholesterol, the so-called "neurosteroids". To understand... (Review)
Review
New findings over the past decade have shown that the brain has the capability of forming steroids de novo from cholesterol, the so-called "neurosteroids". To understand neurosteroid action in the brain, data on the regio- and temporal-specific synthesis of neurosteroids are needed. Recently, we have demonstrated that the Purkinje cell, a cerebellar neuron, is a major site for neurosteroid formation in a variety of vertebrates. This is the first demonstration of de novo neuronal neurosteroidogenesis in the brain. Since this discovery, organizing actions of neurosteroids are becoming clear by the studies on mammals using the Purkinje cell as an excellent cellular model. In mammals, the Purkinje cell actively synthesizes progesterone de novo from cholesterol during neonatal life, when cerebellar neuronal circuit formation occurs. The Purkinje cell may also produces estradiol in the neonate. Interestingly, both progesterone and estradiol promote dendritic growth, spinogenesis and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such organizing actions may contribute to the formation of cerebellar neuronal circuit during neonatal life. This paper summarizes the advances made in our understanding of the biosynthesis, mode of action and functional significance of neurosteroids in the developing Purkinje cell.
Topics: Animals; Humans; Neurons; Purkinje Cells; Receptors, Steroid; Steroids
PubMed: 17113981
DOI: 10.1016/j.jsbmb.2006.09.015 -
Neuroscience 2005Fast (approximately 160 Hz) cerebellar oscillation has been recently described in different models of ataxic mice, such as mice lacking calcium-binding proteins and in a...
Fast (approximately 160 Hz) cerebellar oscillation has been recently described in different models of ataxic mice, such as mice lacking calcium-binding proteins and in a mouse model of Angelman syndrome. Among them, calretinin-calbindin double knockout mice constitute the best model for evaluating fast oscillations in vivo. The cerebellum of these mice may present long-lasting episodes of very strong and stable local field potential oscillation alternating with the normal non-oscillating state. Spontaneous firing of the Purkinje cells in wild type and double knockout mice largely differs. Indeed, the Purkinje cell firing of the oscillating mutant is characterized by an increased rate and rhythmicity and by the emergence of synchronicity along the parallel fiber axis. To better understand the driving role played by these different parameters on fast cerebellar oscillation, we simultaneously recorded Purkinje cells and local field potential during the induction of general anesthesia by ketamine or pentobarbitone. Both drugs significantly increased Purkinje cell rhythmicity in the absence of oscillation, but they did not lead to Purkinje cell synchronization or to the emergence of fast oscillation. During fast oscillation episodes, ketamine abolished Purkinje cell synchronicity and inhibited fast oscillation. In contrast, pentobarbitone facilitated fast oscillation, induced and increased Purkinje cell synchronicity. We propose that fast cerebellar oscillation is due to the synchronous rhythmic firing of Purkinje cell populations and is facilitated by positive feedback whereby the oscillating field further phase-locks recruited Purkinje cells onto the same rhythmic firing pattern.
Topics: Anesthetics, Dissociative; Animals; Calbindin 2; Calbindins; Cortical Synchronization; Female; Hypnotics and Sedatives; Ketamine; Male; Membrane Potentials; Mice; Mice, Knockout; Microinjections; Pentobarbital; Periodicity; Purkinje Cells; S100 Calcium Binding Protein G
PubMed: 16054763
DOI: 10.1016/j.neuroscience.2005.06.001 -
Science (New York, N.Y.) Jul 2023Canonically, each Purkinje cell (PC) in the adult cerebellum receives only one climbing fiber (CF) from the inferior olive. Underlying current theories of cerebellar...
Canonically, each Purkinje cell (PC) in the adult cerebellum receives only one climbing fiber (CF) from the inferior olive. Underlying current theories of cerebellar function is the notion that this highly conserved one-to-one relationship renders Purkinje dendrites into a single computational compartment. However, we discovered that multiple primary dendrites are a near-universal morphological feature in humans. Using tract tracing, immunolabeling, and in vitro electrophysiology, we found that in mice ~25% of mature multibranched cells receive more than one CF input. Two-photon calcium imaging in vivo revealed that separate dendrites can exhibit distinct response properties to sensory stimulation, indicating that some multibranched cells integrate functionally independent CF-receptive fields. These findings indicate that PCs are morphologically and functionally more diverse than previously thought.
Topics: Animals; Humans; Mice; Axons; Dendrites; Purkinje Cells; Synapses
PubMed: 37499000
DOI: 10.1126/science.adi1024 -
Neurobiology of Learning and Memory Dec 2019The general consensus for learning and memory, including in the cerebellum, is that modification of synaptic strength via long-term potentiation (LTP) or long-term... (Review)
Review
The general consensus for learning and memory, including in the cerebellum, is that modification of synaptic strength via long-term potentiation (LTP) or long-term depression (LTD) are the primary mechanisms for the formation of memories. Recent findings suggest additional cellular mechanisms - referred to as 'intrinsic plasticity' - where a neuron's membrane excitability intrinsically changes. These mechanisms act like a dimmer and alter neuronal responsiveness by adjusting response amplitudes and spike thresholds. Here, I argue that classical conditioning of cerebellar Purkinje cell responses reveals yet another cell-intrinsic learning mechanism which significantly differs from both changes in synaptic strength and changes in membrane excitability. When the conditional (CS) and unconditional stimuli (US) are delivered directly to the Purkinje cell's immediate pre-synaptic afferents, the parallel fibres and the climbing fibre, the cell learns to respond to the CS with a pause in its spontaneous firing that reflects the interval between the two stimuli. The pause response has a delayed onset and adaptively timed maximum, offset and duration, determined by the previously experienced CS-US interval. The timing is not dependent on any network-generated time-varying input. This implies the existence of a timing mechanism and a memory substrate that encodes the duration of the CS-US interval inside the Purkinje cell. Such temporal interval learning is not simply a change that causes more or less firing in response to an input. Here, I review these findings in relation to the standard theory of synaptic strength changes and the network interactions believed to be necessary for generating time codes.
Topics: Animals; Cerebellum; Conditioning, Eyelid; Neuronal Plasticity; Purkinje Cells
PubMed: 31648018
DOI: 10.1016/j.nlm.2019.107103 -
Brain Research. Molecular Brain Research Dec 2004The identification of mRNAs that have restricted expression patterns in the brain represents powerful tools with which to characterize and manipulate the nervous system....
The identification of mRNAs that have restricted expression patterns in the brain represents powerful tools with which to characterize and manipulate the nervous system. Here, we describe a strategy using microarray technology (Affymetrix Mouse Genome 430 2.0 Arrays) to identify mRNA transcripts that are candidate markers of cerebellar Purkinje neurons. Initially, gene expression profiles were compared between cerebella of 4-month-old Purkinje cell degeneration (pcd(3J)) mice, in which most Purkinje cells had already degenerated and wild-type littermates with a normal complement of Purkinje neurons. Of 14,563 probe sets expressed in wild-type cerebellum, 797 showed a significant (p<0.0001) reduction in pcd(3J) mice. These probes could represent transcripts with varying levels of specificity for Purkinje cells as well as transcripts in other cell types that decline as a secondary consequence of Purkinje cell loss. Ranking of the probe signals revealed that well-known Purkinje cell-specific transcripts such as calbindin and L7/pcp2 clustered in a group that was <33% of wild-type levels. Therefore, to identify potentially new Purkinje cell-specific transcripts that cluster with the known markers, more stringent selection criteria were applied (<33% of wild-type signal and p<0.0001). With these criteria, 55 independent transcripts were identified of which 33 were annotated genes and 22 were ESTs and RIKEN cDNAs. A literature search revealed that 25 of the 33 annotated genes were expressed in Purkinje cells, with no data being available on the other 8. Thus, the additional 8 annotated and 22 un-annotated genes are clustered with many genes expressed in Purkinje cells making them candidate markers. To confirm the microarray data, eight representative annotated genes were selected including five reported to be in Purkinje neurons and three for which no data was available. Semi-quantitative RT-PCR demonstrated reduced expression of all eight transcripts in cerebella from pcd(3J) mice. The promoters of genes expressed selectively in subsets of neurons can be used to direct heterologous gene expression in transgenic mice and the more restricted the expression pattern the greater their utility. Therefore, microarray analysis was used to assess expression levels of all 55 transcripts in cerebral cortex, striatum, substantia nigra and ventral tegmental area. This permitted the identification of a set of genes whose promoters might have utility for selectively targeting gene expression to cerebellar Purkinje cells.
Topics: Animals; Cerebellum; Genes, Recessive; Genetic Markers; Genotype; Heredodegenerative Disorders, Nervous System; Mice; Mice, Neurologic Mutants; Oligonucleotide Array Sequence Analysis; Purkinje Cells; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 15582153
DOI: 10.1016/j.molbrainres.2004.10.015 -
Journal of Visualized Experiments : JoVE Mar 2012Purkinje cells are an attractive model system for studying dendritic development, because they have an impressive dendritic tree which is strictly oriented in the...
Purkinje cells are an attractive model system for studying dendritic development, because they have an impressive dendritic tree which is strictly oriented in the sagittal plane and develops mostly in the postnatal period in small rodents (3). Furthermore, several antibodies are available which selectively and intensively label Purkinje cells including all processes, with anti-Calbindin D28K being the most widely used. For viewing of dendrites in living cells, mice expressing EGFP selectively in Purkinje cells (11) are available through Jackson labs. Organotypic cerebellar slice cultures cells allow easy experimental manipulation of Purkinje cell dendritic development because most of the dendritic expansion of the Purkinje cell dendritic tree is actually taking place during the culture period (4). We present here a short, reliable and easy protocol for viewing and analyzing the dendritic morphology of Purkinje cells grown in organotypic cerebellar slice cultures. For many purposes, a quantitative evaluation of the Purkinje cell dendritic tree is desirable. We focus here on two parameters, dendritic tree size and branch point numbers, which can be rapidly and easily determined from anti-calbindin stained cerebellar slice cultures. These two parameters yield a reliable and sensitive measure of changes of the Purkinje cell dendritic tree. Using the example of treatments with the protein kinase C (PKC) activator PMA and the metabotropic glutamate receptor 1 (mGluR1) we demonstrate how differences in the dendritic development are visualized and quantitatively assessed. The combination of the presence of an extensive dendritic tree, selective and intense immunostaining methods, organotypic slice cultures which cover the period of dendritic growth and a mouse model with Purkinje cell specific EGFP expression make Purkinje cells a powerful model system for revealing the mechanisms of dendritic development.
Topics: Animals; Cerebellum; Dendrites; Mice; Organ Culture Techniques; Purkinje Cells
PubMed: 22473312
DOI: 10.3791/3637