scholarly journals A spiking network model of cerebellar Purkinje cells and molecular layer interneurons exhibiting irregular firing

2014 ◽  
Vol 8 ◽  
Author(s):  
William Lennon ◽  
Robert Hecht-Nielsen ◽  
Tadashi Yamazaki
Keyword(s):  
Purkinje Cells ◽  
Network Model ◽  
Molecular Layer ◽  
Spiking Network ◽  
Cerebellar Purkinje Cells ◽  
Irregular Firing

scholarly journals Mice With Monoallelic GNAO1 Loss Exhibit Reduced Inhibitory Synaptic Input To Cerebellar Purkinje Cells

2021 ◽  
Author(s):  
Huijie Feng ◽  
Yukun Yuan ◽  
Michael R Williams ◽  
Alex Roy ◽  
Jeffrey Leipprandt ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Purkinje Cells ◽  
Gabab Receptor ◽  
Molecular Layer ◽  
Loss Of Function ◽  
Whole Cell Patch Clamp ◽  
The Difference ◽  
G Protein Alpha Subunit ◽  
Cerebellar Purkinje Cells

GNAO1 encodes Gαo, a heterotrimeric G protein alpha subunit in the Gi/o family. In this report, we used a Gnao1 mouse model G203R previously described as a gain-of-function Gnao1 mutant with movement abnormalities and enhanced seizure susceptibility. Here, we report an unexpected second mutation resulting in a loss-of-function Gαo protein and describe alterations in central synaptic transmission. Whole cell patch clamp recordings from Purkinje cells (PCs) in acute cerebellar slices from Gnao1 mutant mice showed significantly lower frequencies of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) compared to WT mice. There was no significant change in sEPSCs or mEPSCs. Whereas mIPSC frequency was reduced, mIPSC amplitudes were not affected, suggesting a presynaptic mechanism of action. A modest decrease in the number of molecular layer interneurons was insufficient to explain the magnitude of IPSC suppression. Paradoxically, Gi/o inhibitors (pertussis toxin), enhanced the mutant-suppressed mIPSC frequency and eliminated the difference between WT and Gnao1 mice. While GABAB receptor regulates mIPSCs, neither agonists nor antagonists of this receptor altered function in the mutant mouse PCs. This study is the first electrophysiological investigation of the role of Gi/o protein in cerebellar synaptic transmission using an animal model with a loss-of-function Gi/o protein.

scholarly journals Selective loss of the GABAAα1 subunit from Purkinje cells is sufficient to induce a tremor phenotype

2019 ◽  
Author(s):  
Angela Nietz ◽  
Chris Krook-Magnuson ◽  
Haruna Gutierrez ◽  
Julia Klein ◽  
Clarke Sauve ◽  
...  
Keyword(s):  
Essential Tremor ◽  
Purkinje Cells ◽  
Molecular Layer ◽  
Survival Rates ◽  
Motor Deficits ◽  
Gross Motor ◽  
Knock Out ◽  
Background Strain ◽  
Selective Loss ◽  
Cerebellar Purkinje Cells

AbstractBackgroundIncreased circuit level insights into Essential tremor, the most prevalent movement disorder, are needed. Previously, an Essential Tremor-like phenotype was noted in animals with a global knockout of the GABAAα1 subunit. However, global knockout of the GABAAα1 subunit has limitations, including potential early mortality and limited circuit level insights into the tremor.MethodsGiven the hypothesized role of the cerebellum in tremor, including Essential Tremor, we used transgenic mice to selectively knock out the GABAAα1 subunit from cerebellar Purkinje cells. As previous work suggested background strain may influence phenotype in this model, we used two different background strains (a Black6 and a Mixed background). We examined the resulting phenotype regarding impacts on inhibitory postsynaptic currents, survival rates, gross motor abilities, and expression of tremor.ResultsWe found that GABAA-mediated synaptic currents are abolished in Purkinje cells from Purkinje cell specific knockout mice, while GABAA-mediated inhibition to cerebellar molecular layer interneurons remains intact. Selective loss of GABAAα1 from Purkinje cells did not produce gross motor deficits, as measured by the accelerating rotarod, nor did it result in decreased survival rates. However, a tremor phenotype was apparent, regardless of sex or background strain. This tremor mimicked the tremor seen in animals with a global knockout of the GABAAα1 subunit, and, like Essential Tremor in patients, was responsive to ethanol.ConclusionsThese findings indicate that reduced inhibition to Purkinje cells is sufficient to induce a tremor phenotype, highlighting the importance of the cerebellum, inhibition, and Purkinje cells, in tremor.

scholarly journals GluD2- and Cbln1-mediated Competitive Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells

2020 ◽  
Author(s):  
Yukari H. Takeo ◽  
S. Andrew Shuster ◽  
Linnie Jiang ◽  
Miley Hu ◽  
David J. Luginbuhl ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Synapse Formation ◽  
Granule Cells ◽  
Molecular Layer ◽  
Mammalian Brain ◽  
Dependent Manner ◽  
Genetic Epistasis ◽  
Cerebellar Purkinje Cells ◽  
Dendrite Morphogenesis

SUMMARYThe synaptotrophic hypothesis posits that synapse formation stabilizes dendritic branches, yet this hypothesis has not been causally tested in vivo in the mammalian brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2 mediate synaptogenesis between granule cells and Purkinje cells in the molecular layer of the cerebellar cortex. Here we show that sparse but not global knockout of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular layer and overelaboration in the superficial molecular layer. Developmental, overexpression, structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner. A generative model of dendritic growth based on competitive synaptogenesis largely recapitulates GluD2 sparse and global knockout phenotypes. Our results support the synaptotrophic hypothesis at initial stages of dendrite development, suggest a second mode in which cumulative synapse formation inhibits further dendrite growth, and highlight the importance of competition in dendrite morphogenesis.

Voltage-Gated Sodium Channels in Cerebellar Purkinje Cells of Mormyrid Fish

2006 ◽  
Vol 96 (1) ◽  
pp. 378-390 ◽  
Author(s):  
Martijn M. de Ruiter ◽  
Chris I. De Zeeuw ◽  
Christian Hansel
Keyword(s):  
Purkinje Cells ◽  
Molecular Layer ◽  
Climbing Fiber ◽  
Excitatory Postsynaptic Potential ◽  
Electrophysiological Response ◽  
Voltage Gated ◽  
Response Characteristics ◽  
Mormyrid Fish ◽  
Cerebellar Purkinje Cells ◽  
Immunohistochemical Techniques

Cerebellar Purkinje cells of mormyrid fish differ in some morphological as well as physiological parameters from their counterparts in mammals. Morphologically, Purkinje cells of mormyrids have larger dendrites that are characterized by a lower degree of branching in the molecular layer. Physiologically, there are differences in electrophysiological response patterns that are related to sodium channel activity: first, sodium spikes in mormyrid Purkinje cells have low amplitudes, typically not exceeding 30 mV. Second, the response to climbing fiber stimulation in mormyrid Purkinje cells does not consist of a complex spike (with an initial fast sodium spike) as in mammals, but instead it consists of an all-or-none excitatory postsynaptic potential, the so-called climbing fiber response. Because of these unique properties, we have begun to characterize mormyrid Purkinje cells electrophysiologically. In this study, we provide a description of voltage-gated Na+ channels and conductances in Purkinje cells of the mormyrid fish Gnathonemus petersii. Various types of Na+ channel α-subunits, i.e., Nav1.1, Nav1.2, and Nav1.6, have been described in rodent Purkinje cells. Using immunohistochemical techniques, we found that these subunits are present in Purkinje cells of mormyrids. To test whether these Na+ channel subunits can mediate fast inactivating and resurgent Na+ currents in Gnathonemus Purkinje cells, we conducted patch-clamp recordings in acutely dissociated cells and in cerebellar slices. Both types of Na+ currents could be measured in rat and fish Purkinje cells. These data show that, despite prominent differences in electrophysiological response characteristics, Purkinje cells of rats and mormyrids share the same voltage-gated Na+ conductances.

scholarly journals Molecular layer interneurons shape the spike activity of cerebellar Purkinje cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amanda M. Brown ◽  
Marife Arancillo ◽  
Tao Lin ◽  
Daniel R. Catt ◽  
Joy Zhou ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Spike Activity ◽  
Molecular Layer ◽  
Cerebellar Purkinje Cells

Ultrastorcture of Cerebellar Purkinje Cells in Rats Subjected To Partial Global Cerebral Ischemia

1985 ◽  
Vol 43 ◽  
pp. 674-675
Author(s):  
R.V.W. Dimlich ◽  
M.H. Biros
Keyword(s):  
Cerebral Ischemia ◽  
Purkinje Cells ◽  
Cell Types ◽  
Microscopic Level ◽  
Global Cerebral Ischemia ◽  
Light Microscopic Level ◽  
Cerebellar Damage ◽  
Cerebellar Injury ◽  
Cerebellar Purkinje Cells ◽  
Cell Changes

In severe cerebral ischemia, Purkinje cells of the cerebellum are one of the cell types most vulnerable to anoxic damage. In the partial (forebrain) global ischemic (PGI) model of the rat, Paljärvi noted at the light microscopic level that cerebellar damage is inconsistant and when present, milder than in the telencephalon, diencephalon and rostral brain stem. Cerebellar injury was observed in 3 of 4 PGI rats following 5 minutes of reperfusion but in none of the rats after 90 min of reperfusion. To evaluate a time between these two extremes (5 and 90 min), the present investigation used the PGI model to study the effects of ischemia on the ultrastructure of cerebellar Purkinje cells in rats that were sacrificed after 30 min of reperfusion. This time also was chosen because lactic acid that is thought to contribute to ischemic cell changes in PGI is at a maximum after 30 min of reperfusion.

Ultrasturcture of cerebellar cells and neuropil in rats subjected to partial global cerebral ischemia

1986 ◽  
Vol 44 ◽  
pp. 126-127
Author(s):  
R.V.W. Dimlich ◽  
M.H. Biros
Keyword(s):  
Purkinje Cells ◽  
Glial Cells ◽  
Granule Cells ◽  
Molecular Layer ◽  
Cell Types ◽  
Primary Objective ◽  
Global Cerebral Ischemia ◽  
Forebrain Ischemia ◽  
Substantial Evidence ◽  
Cerebellar Cells

Although a previous study in this laboratory determined that Purkinje cells of the rat cerebellum did not appear to be damaged following 30 min of forebrain ischemia followed by 30 min of reperfusion, it was suggested that an increase in rough endoplasmic reticulum (RER) and/or polysomes had occurred in these cells. The primary objective of the present study was to morphometrically determine whether or not this increase had occurred. In addition, since there is substantial evidence that glial cells may be affected by ischemia earlier than other cell types, glial cells also were examined. To ascertain possible effects on other cerebellar components, granule cells and neuropil near Purkinje cells as well as neuropil in the molecular layer also were evaluated in this investigation.

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