Purkinje cells located in the adult zebrafish valvula cerebelli exhibit variable functional responses

AbstractPurkinje cells are critically involved in processing the cerebellar functions by shaping and coordinating commands that they receive. Here, we demonstrate experimentally that in the adult zebrafish valvular part of the cerebellum, the Purkinje cells exhibited variable firing and functional responses and allowed the categorization into three firing classes. Compared with the Purkinje cells in the corpus cerebelli, the valvular Purkinje cells receive weak and occasional input from the inferior olive and are not active during locomotion. Together, our findings expand further the regional functional differences of the Purkinje cell population and expose their non-locomotor functionality.

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Functionally distinct Purkinje cell types show temporal precision in encoding locomotion

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2005633117 ◽

2020 ◽

Vol 117 (29) ◽

pp. 17330-17337

Author(s):

Weipang Chang ◽

Andrea Pedroni ◽

Victoria Hohendorf ◽

Stefania Giacomello ◽

Masahiko Hibi ◽

...

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Central Pattern Generators ◽

Cell Types ◽

Neuronal Population ◽

Adult Zebrafish ◽

Temporal Precision ◽

Distinct Cell ◽

Pattern Generators ◽

Cell Networks

Purkinje cells, the principal neurons of cerebellar computations, are believed to comprise a uniform neuronal population of cells, each with similar functional properties. Here, we show an undiscovered heterogeneity of adult zebrafish Purkinje cells, revealing the existence of anatomically and functionally distinct cell types. Dual patch-clamp recordings showed that the cerebellar circuit contains all Purkinje cell types that cross-communicate extensively using chemical and electrical synapses. Further activation of spinal central pattern generators (CPGs) revealed unique phase-locked activity from each Purkinje cell type during the locomotor cycle. Thus, we show intricately organized Purkinje cell networks in the adult zebrafish cerebellum that encode the locomotion rhythm differentially, and we suggest that these organizational properties may also apply to other cerebellar functions.

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Distribution of cortactin in cerebellar Purkinje cell spines

Scientific Reports ◽

10.1038/s41598-020-80469-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lilla E. Szabó ◽

G. Mark Marcello ◽

Miklós Süth ◽

Péter Sótonyi ◽

Bence Rácz

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Dendritic Spines ◽

Mammalian Brain ◽

Synaptic Membrane ◽

Branch Points ◽

Excitatory Transmission ◽

Functional Differences ◽

Cerebellar Purkinje Cells ◽

Spine Plasticity

AbstractDendritic spines are the primary sites of excitatory transmission in the mammalian brain. Spines of cerebellar Purkinje Cells (PCs) are plastic, but they differ from forebrain spines in a number of important respects, and the mechanisms of spine plasticity differ between forebrain and cerebellum. Our previous studies indicate that in hippocampal spines cortactin—a protein that stabilizes actin branch points—resides in the spine core, avoiding the spine shell. To see whether the distribution of cortactin differs in PC spines, we examined its subcellular organization using quantitative preembedding immunoelectron microscopy. We found that cortactin was enriched in the spine shell, associated with the non-synaptic membrane, and was also situated within the postsynaptic density (PSD). This previously unrecognized distribution of cortactin within PC spines may underlie structural and functional differences in excitatory spine synapses between forebrain, and cerebellum.

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Ethanol effects on the olivocerebellar system

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y82-082 ◽

1982 ◽

Vol 60 (5) ◽

pp. 610-614 ◽

Cited By ~ 14

Author(s):

J. G. Sinclair ◽

G. F. Lo ◽

D. P. Harris

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Inferior Olive ◽

Climbing Fibre ◽

Complex Spike ◽

Anaesthetized Rats ◽

Cerebellar Purkinje Cells ◽

Cell Synapse

Ethanol (1.5 g/kg i.v.) was found to decrease spontaneous complex spike (CS) activity in cerebellar Purkinje cells in urethane anaesthetized rats while not changing the threshold required to evoke a CS by juxtafastigial stimulation. Thus ethanol does not decrease CS activity by an action at the climbing fibre – Purkinje cell synapse. Tremor induced by harmaline (5 mg/kg i.v.) in unanaesthetized animals was markedly antagonized by ethanol (0.5–2.0 g/kg i.v.) in all animals tested. However, in nine urethane-anaesthetized animals, ethanol markedly reversed the effects of harmaline on Purkinje cells in only two cases and partially reversed the effects in another four cells. Thus, the depressant effects of ethanol on the inferior olive is not totally responsible for the blockade of the harmaline tremor but would account for the decrease in spontaneous CS activity.

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Association Between Dendritic Lamellar Bodies and Complex Spike Synchrony in the Olivocerebellar System

Journal of Neurophysiology ◽

10.1152/jn.1997.77.4.1747 ◽

1997 ◽

Vol 77 (4) ◽

pp. 1747-1758 ◽

Cited By ~ 45

Author(s):

C. I. De Zeeuw ◽

S.K.E. Koekkoek ◽

D.R.W. Wylie ◽

J. I. Simpson

Keyword(s):

Purkinje Cell ◽

Gap Junctions ◽

Purkinje Cells ◽

Inferior Olive ◽

Cerebellar Nuclei ◽

Climbing Fibers ◽

Lamellar Bodies ◽

Spike Synchrony ◽

Complex Spike ◽

Simple Spike

De Zeeuw, C. I., S.K.E. Koekkoek, D.R.W. Wylie, and J. I. Simpson. Association between dendritic lamellar bodies and complex spike synchrony in the olivocerebellar system. J. Neurophysiol. 77: 1747–1758, 1997. Dendritic lamellar bodies have been reported to be associated with dendrodendritic gap junctions. In the present study we investigated this association at both the morphological and electrophysiological level in the olivocerebellar system. Because cerebellar GABAergic terminals are apposed to olivary dendrites coupled by gap junctions, and because lesions of cerebellar nuclei influence the coupling between neurons in the inferior olive, we postulated that if lamellar bodies and gap junctions are related, then the densities of both structures will change together when the cerebellar input is removed. Lesions of the cerebellar nuclei in rats and rabbits resulted in a reduction of the density of lamellar bodies, the number of lamellae per lamellar body, and the density of gap junctions in the inferior olive, whereas the number of olivary neurons was not significantly reduced. The association between lamellar bodies and electrotonic coupling was evaluated electrophysiologically in alert rabbits by comparing the occurrence of complex spike synchrony in different Purkinje cell zones of the flocculus that receive their climbing fibers from olivary subnuclei with different densities of lamellar bodies. The complex spike synchrony of Purkinje cell pairs, that receive their climbing fibers from an olivary subnucleus with a high density of lamellar bodies, was significantly higher than that of Purkinje cells, that receive their climbing fibers from a subnucleus with a low density of lamellar bodies. To investigate whether the complex spike synchrony is related to a possible synchrony between simple spikes, we recorded simultaneously the complex spike and simple spike responses of Purkinje cell pairs during natural visual stimulation. Synchronous simple spike responses did occur, and this synchrony tended to increase as the synchrony between the complex spikes increased. This relation raises the possibility that synchronously activated climbing fibers evoke their effects in part via the simple spike response of Purkinje cells. The present results indicate that dendritic lamellar bodies and dendrodendritic gap junctions can be downregulated concomitantly, and that the density of lamellar bodies in different olivary subdivisions is correlated with the degree of synchrony of their climbing fiber activity. Therefore these data support the hypothesis that dendritic lamellar bodies can be associated with dendrodendritic gap junctions. Considering that the density of dedritic lamellar bodies in the inferior olive is higher than in any other area of the brain, this conclusion implies that electrotonic coupling is important for the function of the olivocerebellar system.

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Decrement of the Purkinje Cells Diameter after Oral Intake of Lithium in Albino Rats

10.53350/pjmhs211581788 ◽

2021 ◽

Vol 15 (8) ◽

pp. 1788-1789

Author(s):

Tazeen Kohari ◽

Farah Malik ◽

Aftab Ahmad

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Gray Matter ◽

Oral Intake ◽

Lithium Carbonate ◽

Albino Rats ◽

Cell Diameter ◽

Group A ◽

Cerebellar Gray Matter ◽

Group B

Background: The histology of Cerebellar gray matter consists of a middle Purkinje cells layer with flask shaped Purkinje cells. The field of Neurology has documented that different organic compounds and metals are lethal to the excitatory Purkinje Neurons. Researches have proved Lithium to be hazardous to nervous tissue and especially Cerebellum For the past sixty years Lithium is the favorable drug for treatment of Bipolar Disorder. Aim: To Analyse and record the changes of decrement of the size of Purkinje cell Diameter after chronic Lithium ingestion. Methods: Sixteen albino rats were selected and were treated with lithium for a period of fifteen days and the data for changes in Purkinje cells Diameter was observed. Results: The Observations of Our study showed highly significantly decreased diameter of the Purinje cells in Group B (Lithium Carbonate) animals as compared to Group A Animals which were on Lab Diet Conclusion: The Morphometric Data proved that Lithium Carbonate is Toxic to Purkinje cells, and it educated our Population to use Lithium with caution. Keywords: Purkinje cell Diameter, Gray matter, Hazardous

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The induction of multiple cell cycle events precedes target-related neuronal death

Development ◽

10.1242/dev.121.8.2385 ◽

1995 ◽

Vol 121 (8) ◽

pp. 2385-2395 ◽

Cited By ~ 1

Author(s):

K. Herrup ◽

J.C. Busser

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Purkinje Cell ◽

Inferior Olive ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Ventricular Zone ◽

Nuclear Antigen ◽

Electron Microscopic ◽

Related Cell

Unexpected nerve cell death has been reported in several experimental situations where neurons have been forced to re-enter the cell cycle after leaving the ventricular zone and entering the G0, non-mitotic stage. To determine whether an association between cell death and unscheduled cell cycling might be found in conjunction with any naturally occurring developmental events, we have examined target-related cell death in two neuronal populations, the granule cells of the cerebellar cortex and the neurons of the inferior olive. Both of these cell populations have a demonstrated developmental dependency on their synaptic target, the cerebellar Purkinje cell. Two mouse neurological mutants, staggerer (sg/sg) and lurcher (+/Lc), are characterized by intrinsic Purkinje cell deficiencies and, in both mutants, substantial numbers of cerebellar granule cells and inferior olive neurons die due to the absence of trophic support from their main postsynaptic target. We report here that the levels of three independent cell cycle markers--cyclin D, proliferating cell nuclear antigen and bromodeoxyuridine incorporation--are elevated in the granule cells before they die. Although lurcher Purkinje cells die during a similar developmental period, no compelling evidence for any cell cycle involvement in this instance of pre-programmed cell death could be found. While application of the TUNEL technique (in situ terminal transferase end-labeling of fragmented DNA) failed to label dying granule cells in either mutant, light and electron microscopic observations are consistent with the interpretation that the death of these cells is apoptotic in nature. Together, the data indicate that target-related cell death in the developing central nervous system is associated with a mechanism of cell death that involves an apparent loss of cell cycle control.

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Activation of MAP3K DLK and LZK in Purkinje Cells Causes Rapid and Slow Degeneration Depending on Signaling Strength

10.1101/2020.10.09.332940 ◽

2020 ◽

Author(s):

Yunbo Li ◽

Erin M Ritchie ◽

Christopher L. Steinke ◽

Cai Qi ◽

Lizhen Chen ◽

...

Keyword(s):

Alternative Splicing ◽

Purkinje Cell ◽

Purkinje Cells ◽

Leucine Zipper ◽

Activity Levels ◽

Cell Type ◽

Cell Degeneration ◽

Mechanistic Basis ◽

Cerebellar Purkinje Cells ◽

Jnk Activation

SummaryThe conserved MAP3K Dual leucine zipper kinases can activate JNK via MKK4 or MKK7. Vertebrate DLK and LZK share similar biochemical activities and undergo auto-activation upon increased expression. Depending on cell-type and nature of insults DLK and LZK can induce pro-regenerative, pro-apoptotic or pro-degenerative responses, although the mechanistic basis of their action is not well understood. Here, we investigated these two MAP3Ks in cerebellar Purkinje cells using loss- and gain-of function mouse models. While loss of each or both kinases does not cause discernible defects in Purkinje cells, activating DLK causes rapid death and activating LZK leads to slow degeneration. Each kinase induces JNK activation and caspase-mediated apoptosis independent of each other. Significantly, deleting CELF2, which regulates alternative splicing of Mkk7, strongly attenuates Purkinje cell degeneration induced by activation of LZK, but not DLK. Thus, controlling the activity levels of DLK and LZK is critical for neuronal survival and health.

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Cerebellar and vestibular nuclear synapses in the inferior olive have distinct release kinetics and neurotransmitters

eLife ◽

10.7554/elife.61672 ◽

2020 ◽

Vol 9 ◽

Author(s):

Josef Turecek ◽

Wade G Regehr

Keyword(s):

Purkinje Cells ◽

Inferior Olive ◽

Release Kinetics ◽

Vestibular Nuclei ◽

Cerebellar Nuclei ◽

Climbing Fiber ◽

Inhibitory Input ◽

Deep Cerebellar Nuclei

The inferior olive (IO) is composed of electrically-coupled neurons that make climbing fiber synapses onto Purkinje cells. Neurons in different IO subnuclei are inhibited by synapses with wide ranging release kinetics. Inhibition can be exclusively synchronous, asynchronous, or a mixture of both. Whether the same boutons, neurons or sources provide these kinetically distinct types of inhibition was not known. We find that in mice the deep cerebellar nuclei (DCN) and vestibular nuclei (VN) are two major sources of inhibition to the IO that are specialized to provide inhibitory input with distinct kinetics. DCN to IO synapses lack fast synaptotagmin isoforms, release neurotransmitter asynchronously, and are exclusively GABAergic. VN to IO synapses contain fast synaptotagmin isoforms, release neurotransmitter synchronously, and are mediated by combined GABAergic and glycinergic transmission. These findings indicate that VN and DCN inhibitory inputs to the IO are suited to control different aspects of IO activity.

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Purkinje Cell Collaterals Enable Output Signals from the Cerebellar Cortex to Feed Back to Purkinje Cells and Interneurons

Neuron ◽

10.1016/j.neuron.2016.05.037 ◽

2016 ◽

Vol 91 (2) ◽

pp. 312-319 ◽

Cited By ~ 59

Author(s):

Laurens Witter ◽

Stephanie Rudolph ◽

R. Todd Pressler ◽

Safiya I. Lahlaf ◽

Wade G. Regehr

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Cerebellar Cortex

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Preterm Birth Impedes Structural and Functional Development of Cerebellar Purkinje Cells in the Developing Baboon Cerebellum

Brain Sciences ◽

10.3390/brainsci10120897 ◽

2020 ◽

Vol 10 (12) ◽

pp. 897

Author(s):

Tara Barron ◽

Jun Hee Kim

Keyword(s):

Preterm Birth ◽

Action Potential ◽

Purkinje Cell ◽

Purkinje Cells ◽

Late Gestation ◽

Cerebellar Development ◽

Layer Width ◽

Action Potential Waveform ◽

Developmental Features ◽

Potential Waveform

Human cerebellar development occurs late in gestation and is hindered by preterm birth. The fetal development of Purkinje cells, the primary output cells of the cerebellar cortex, is crucial for the structure and function of the cerebellum. However, morphological and electrophysiological features in Purkinje cells at different gestational ages, and the effects of neonatal intensive care unit (NICU) experience on cerebellar development are unexplored. Utilizing the non-human primate baboon cerebellum, we investigated Purkinje cell development during the last trimester of pregnancy and the effect of NICU experience following premature birth on developmental features of Purkinje cells. Immunostaining and whole-cell patch clamp recordings of Purkinje cells in the baboon cerebellum at different gestational ages revealed that molecular layer width, driven by Purkinje dendrite extension, drastically increased and refinement of action potential waveform properties occurred throughout the last trimester of pregnancy. Preterm birth followed by NICU experience for 2 weeks impeded development of Purkinje cells, including action potential waveform properties, synaptic input, and dendrite extension compared with age-matched controls. In addition, these alterations impact Purkinje cell output, reducing the spontaneous firing frequency in deep cerebellar nucleus (DCN) neurons. Taken together, the primate cerebellum undergoes developmental refinements during late gestation, and NICU experience following extreme preterm birth influences morphological and physiological features in the cerebellum that can lead to functional deficits.

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