scholarly journals Ethanol effects on the olivocerebellar system

1982 ◽  
Vol 60 (5) ◽  
pp. 610-614 ◽  
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.

scholarly journals Neurons of the inferior olive respond to broad classes of sensory input while subject to homeostatic control

2018 ◽  
Author(s):  
Chiheng Ju ◽  
Laurens W.J. Bosman ◽  
Tycho M. Hoogland ◽  
Arthiha Velauthapillai ◽  
Pavithra Murugesan ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Inferior Olive ◽  
Recent History ◽  
Climbing Fibre ◽  
Homeostatic Control ◽  
Complex Spike ◽  
History Of ◽  
Sensory Evoked ◽  
Complex Spikes ◽  
Spike Firing

AbstractCerebellar Purkinje cells integrate sensory information with motor efference copies to adapt movements to behavioural and environmental requirements. They produce complex spikes that are triggered by the activity of climbing fibres originating in neurons of the inferior olive. These complex spikes can shape the onset, amplitude and direction of movements as well as the adaptation of such movements to sensory feedback. Clusters of nearby inferior olive neurons project to parasagittally aligned stripes of Purkinje cells, referred to as “microzones”. It is currently unclear to what extent individual Purkinje cells within a single microzone integrate climbing fibre inputs from multiple sources of different sensory origins, and to what extent sensory-evoked climbing fibre responses depend on the strength and recent history of activation. Here we imaged complex spike responses in cerebellar lobule crus 1 to various types of sensory stimulation in awake mice. We find that different sensory modalities and receptive fields have a mild, but consistent, tendency to converge on individual Purkinje cells. Purkinje cells encoding the same stimulus show increased events with coherent complex spike firing and tend to lie close together. Moreover, whereas complex spike firing is only mildly affected by variations in stimulus strength, it strongly depends on the recent history of climbing fibre activity. Our data point towards a mechanism in the olivo-cerebellar system that regulates complex spike firing during mono- or multisensory stimulation around a relatively low set-point, highlighting an integrative coding scheme of complex spike firing under homeostatic control.

The effects of ethanol on cerebellar Purkinje cells in naive and alcohol-dependent rats

1980 ◽  
Vol 58 (4) ◽  
pp. 429-432 ◽  
Author(s):  
J. G. Sinclair ◽  
G. F. Lo ◽  
A. F. Tien
Keyword(s):  
Purkinje Cells ◽  
Acute Tolerance ◽  
Climbing Fibre ◽  
Anaesthetized Rats ◽  
Cerebellar Purkinje Cells ◽  
Alcohol Dependent

In urethane-anaesthetized rats, ethanol (1.5 g/kg, i.v.) increased the rate of discharge of cerebellar Purkinje cells, increased their regularity of discharge, and reduced or eliminated the climbing fibre evoked bursts. Most of the neurones responding in this manner exhibited an acute tolerance to the drug. Another group of rats was made alcohol dependent by feeding them for 2 weeks on a diet containing ethanol (12.5–16.5 g/kg per day). Ethanol produced similar but reduced effects on Purkinje cells of these animals.

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

1997 ◽  
Vol 77 (4) ◽  
pp. 1747-1758 ◽  
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.

scholarly journals Using deep neural networks to detect complex spikes of cerebellar Purkinje Cells

2019 ◽  
Author(s):  
Akshay Markanday ◽  
Joachim Bellet ◽  
Marie E. Bellet ◽  
Ziad M. Hafed ◽  
Peter Thier
Keyword(s):  
Motor Control ◽  
Deep Learning ◽  
Action Potential ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Local Field ◽  
Visual Inspection ◽  
Complex Spike ◽  
Cerebellar Purkinje Cells ◽  
Complex Spikes

AbstractOne of the most powerful excitatory synapses in the entire brain is formed by cerebellar climbing fibers, originating from neurons in the inferior olive, that wrap around the proximal dendrites of cerebellar Purkinje cells. The activation of a single olivary neuron is capable of generating a large electrical event, called “complex spike”, at the level of the postsynaptic Purkinje cell, comprising of a fast initial spike of large amplitude followed by a slow polyphasic tail of small amplitude spikelets. Several ideas discussing the role of the cerebellum in motor control are centered on these complex spike events. However, these events are extremely rare, only occurring 1-2 times per second. As a result, drawing conclusions about their functional role has been very challenging, as even few errors in their detection may change the result. Since standard spike sorting approaches cannot fully handle the polyphasic shape of complex spike waveforms, the only safe way to avoid omissions and false detections has been to rely on visual inspection of long traces of Purkinje cell recordings by experts. Here we present a supervised deep learning algorithm for rapidly and reliably detecting complex spikes as an alternative to tedious visual inspection. Our algorithm, utilizing both action potential and local field potential signals, not only detects complex spike events much faster than human experts, but it also excavates key features of complex spike morphology with a performance comparable to that of such experts.Significance statementClimbing fiber driven “complex spikes”, fired at perplexingly low rates, are known to play a crucial role in cerebellum-based motor control. Careful interpretations of these spikes require researchers to manually detect them, since conventional online or offline spike sorting algorithms (optimized for analyzing the much more frequent “simple spikes”) cannot be fully trusted. Here, we present a deep learning approach for identifying complex spikes, which is trained on local field and action potential recordings from cerebellar Purkinje cells. Our algorithm successfully identifies complex spikes, along with additional relevant neurophysiological features, with an accuracy level matching that of human experts, yet with very little time expenditure.

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

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.

Nonclock behavior of inferior olive neurons: interspike interval of Purkinje cell complex spike discharge in the awake behaving monkey is random

1995 ◽  
Vol 73 (4) ◽  
pp. 1329-1340 ◽  
Author(s):  
J. G. Keating ◽  
W. T. Thach
Keyword(s):  
Fourier Transform ◽  
Purkinje Cells ◽  
Spike Activity ◽  
Interspike Interval ◽  
Inferior Olive ◽  
Fourier Transforms ◽  
Wrist Movement ◽  
General Role ◽  
Complex Spike ◽  
Bodily Movement

1. Complex spikes of cerebellar Purkinje cells recorded from awake, behaving monkeys were studied to determine the extent to which their discharge could be quantified as periodic. Three Rhesus monkeys were trained to perform up to five different tasks involving rotation of the wrist in relation to a visual cue. Complex spike activity was recorded during task performance and intertrial time. Interspike intervals were determined from the discharge of each of 89 Purkinje cells located throughout lobules IV, V, and VI. Autocorrelation and Fourier transform of the autocorrelation function were performed on the data. In addition, the activity from one cell was transformed so that the discharge occurred on the beat of a 10-Hz clock, and in a further transformation, on the beat of a noisy 10-Hz clock. These transformed data were then analyzed as described above. 2. Fourier transform of the autocorrelogram function of the data that had been transformed to a 10-Hz clock, and that of the noisy 10-Hz clock, both showed a prominent peak at 10 Hz. However, the autocorrelograms and the Fourier transforms of the autocorrelogram functions failed to reveal a prominent periodicity for the actual discharge of any of cells, at any frequency up to 100 Hz: the discharge appeared random with respect to the interspike interval. The discharge was not random with respect to behavior. Complex spike activity was commonly time locked to the start of wrist movement. We examined this discharge to see whether oscillatory discharge could be seen after alignment of the data on the start of wrist movement, or after alignment of the data on the complex spike occurring peri-start of wrist movement. No oscillation was seen for either alignment. 3. The inferior olive, which sends its climbing fibers to the cerebellum, has been implicated in such different activities as 1) pathological tremor of the soft palate, 2) physiological tremor, 3) the normal initiation of all bodily movement, and 4) motor learning. Previous work in pharmacologically or surgically treated animals has shown that, under some conditions, the discharge of these neurons is periodic and synchronous. This firing pattern has been interpreted to support a role in the first two activities. But measurements reported here in the awake monkey show just the opposite: the discharge is aperiodic to the extent of being random. As such, the inferior olive cannot be a "motor clock" in the general role that has been proposed.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of metabotropic glutamate (ACPD) receptors at the parallel fiber-Purkinje cell synapse

1992 ◽  
Vol 68 (4) ◽  
pp. 1453-1462 ◽  
Author(s):  
S. R. Glaum ◽  
N. T. Slater ◽  
D. J. Rossi ◽  
R. J. Miller
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Parallel Fiber ◽  
Membrane Properties ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Fura 2 ◽  
Metabotropic Glutamate ◽  
Cell Synapse

1. The role of metabotropic glutamate receptors at the parallel fiber (PF)-Purkinje cell synapse in cerebellum was studied by examining the actions of the active stereoisomer (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [1S,3R-ACPD (25-50 microM)] on fura-2-loaded, patch-clamped rat Purkinje cells in thin slices. 2. The bath application of 1S,3R-ACPD evoked a direct post-synaptic depolarization that readily desensitized during prolonged (> 1 min) applications of the drug. This depolarizing response to 1S,3R-ACPD differed from the slow depolarization to 1S,3R-ACPD observed in cortical neurons mediated via closure of potassium channels in that it was not associated with an obvious change in membrane conductance and was not blocked by external barium. Similarly, slow inward rectifier currents were not affected during the 1S,3R-ACPD-induced depolarization. 3. The direct depolarization induced by 1S,3R-ACPD was not mediated by N-methyl-D-aspartate (NMDA) or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid kainate (AMPA)-KA excitatory amino acid (EAA) receptor subtypes, because the response was not blocked in the presence of antagonists of these receptors. 4. The EAA antagonist L-2-amino-3-phosphonopropionic acid, which blocks 1S,3R-ACPD-induced inositide synthesis in other cell types, had no effect on the depolarizing response. 5. Fura-2 measurements of somatic [Ca2+]i revealed that [Ca2+]i was not elevated during the 1S,3R-ACPD-induced depolarization unless the cell fired calcium-dependent action potentials. 6. In addition to the direct depolarization induced by 1S,3R-ACPD, the amplitude of PF-evoked excitatory postsynaptic potentials (EPSPs) was profoundly and reversibly reduced. This effect was observed in all cells regardless of whether a direct depolarization was produced by 1S,3R-ACPD. This reduction of the PF EPSP generally preceded the onset of depolarizing responses, did not desensitize during prolonged applications of 1S,3R-ACPD, and was reversible. 7. The reversible reduction of the PF EPSP by 1S,3R-ACPD was not related to a postsynaptic blocking action of the drug, because responses of Purkinje cells to AMPA, an agonist of the EAA receptor subtype mediating the EPSP, were reversibly potentiated in the presence of 1S,3R-ACPD. 8. The nitric oxide synthesis promoter sodium nitroprusside (1-3 nM) had no effect on the amplitude of PF EPSP or the membrane properties of Purkinje cells.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Expression of the yes proto-oncogene in cerebellar Purkinje cells.

1989 ◽  
Vol 9 (10) ◽  
pp. 4545-4549 ◽  
Author(s):  
M Sudol ◽  
C F Kuo ◽  
L Shigemitsu ◽  
A Alvarez-Buylla
Keyword(s):  
In Situ Hybridization ◽  
Purkinje Cell ◽  
Gene Product ◽  
Purkinje Cells ◽  
Immunofluorescent Staining ◽  
Cell Degeneration ◽  
Functional Studies ◽  
Cerebellar Purkinje Cells ◽  
The Brain

To identify the kinds of cells in the brain that express the yes proto-oncogene, we examined chicken brains by using immunofluorescent staining and in situ hybridization. Both approaches showed that the highest level of the yes gene product was in cerebellar Purkinje cells. In addition, we analyzed Purkinje cell degeneration (pcd) mutant mice. The level of yes mRNA in cerebella of pcd mutants was four times lower than that found in cerebella of normal littermates. Our studies point to Purkinje cells as an attractive model for functional studies of the yes protein.

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