scholarly journals Impact of theleanerP/Q-type Ca2+channel mutation on excitatory synaptic transmission in cerebellar Purkinje cells

2008 ◽  
Vol 586 (18) ◽  
pp. 4501-4515 ◽  
Author(s):  
Shaolin Liu ◽  
David D. Friel
Keyword(s):  
Synaptic Transmission ◽  
Purkinje Cells ◽  
Excitatory Synaptic Transmission ◽  
Channel Mutation ◽  
Cerebellar Purkinje Cells

scholarly journals Cannabinoids decrease excitatory synaptic transmission and impair long-term depression in rat cerebellar Purkinje cells

1998 ◽  
Vol 510 (3) ◽  
pp. 867-879 ◽  
Author(s):  
Carole Lévénès ◽  
Hervé Daniel ◽  
Philippe Soubrié ◽  
Françis Crépel
Keyword(s):  
Synaptic Transmission ◽  
Purkinje Cells ◽  
Excitatory Synaptic Transmission ◽  
Long Term Depression ◽  
Cerebellar Purkinje Cells

Kinetic Model of Excitatory Synaptic Transmission to Cerebellar Purkinje Cells

1997 ◽  
Vol 188 (2) ◽  
pp. 227-240 ◽  
Author(s):  
Jörg Marienhagen ◽  
Bernhard U. Keller ◽  
Annette Zippelius
Keyword(s):  
Kinetic Model ◽  
Synaptic Transmission ◽  
Purkinje Cells ◽  
Excitatory Synaptic Transmission ◽  
Cerebellar Purkinje Cells

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 Alteration of GABAergic Input Precedes Neurodegeneration of Cerebellar Purkinje Cells of NPC1-Deficient Mice

2019 ◽  
Vol 20 (24) ◽  
pp. 6288 ◽  
Author(s):  
Michael Rabenstein ◽  
Nico Murr ◽  
Andreas Hermann ◽  
Arndt Rolfs ◽  
Moritz J. Frech
Keyword(s):  
Synaptic Transmission ◽  
Purkinje Cells ◽  
Lysosomal Storage ◽  
Niemann Pick Disease ◽  
Western Blot Testing ◽  
Progressive Neurodegeneration ◽  
Niemann Pick ◽  
Cerebellar Purkinje Cells ◽  
Deficient Mice ◽  
Gabaergic Synaptic Transmission

Niemann-Pick Disease Type C1 (NPC1) is a rare hereditary neurodegenerative disease belonging to the family of lysosomal storage disorders. NPC1-patients suffer from, amongst other symptoms, ataxia, based on the dysfunction and loss of cerebellar Purkinje cells. Alterations in synaptic transmission are believed to contribute to a pathological mechanism leading to the progressive loss of Purkinje cells observed in NPC1-deficient mice. With regard to inhibitory synaptic transmission, alterations of GABAergic synapses are described but functional data are missing. For this reason, we have examined here the inhibitory GABAergic synaptic transmission of Purkinje cells of NPC1-deficient mice (NPC1−/−). Patch clamp recordings of inhibitory post-synaptic currents (IPSCs) of Purkinje cells revealed an increased frequency of GABAergic IPSCs in NPC1−/− mice. In addition, Purkinje cells of NPC1−/− mice were less amenable for modulation of synaptic transmission via the activation of excitatory NMDA-receptors (NMDA-Rs). Western blot testing disclosed a reduced protein level of phosphorylated alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA-Rs) subunit GluA2 in the cerebella of NPC1−/− mice, indicating a disturbance in the internalization of GluA2-containing AMPA-Rs. Since this is triggered by the activation of NMDA-Rs, we conclude that a disturbance in the synaptic turnover of AMPA-Rs underlies the defective inhibitory GABAergic synaptic transmission. While these alterations precede obvious signs of neurodegeneration of Purkinje cells, we propose a contribution of synaptic malfunction to the initiation of the loss of Purkinje cells in NPC1. Thus, a prevention of the disturbance of synaptic transmission in early stages of the disease might display a target with which to avert progressive neurodegeneration in NPC1.

Patch-clamp Analysis of Synaptic Transmission to Cerebellar Purkinje Cells of Prion Protein Knockout Mice

1995 ◽  
Vol 7 (12) ◽  
pp. 2508-2512 ◽  
Author(s):  
Jochen W. Herms ◽  
Hans A. Kretzschmar ◽  
Stefan Titz ◽  
Bernhard U. Keller
Keyword(s):  
Patch Clamp ◽  
Synaptic Transmission ◽  
Prion Protein ◽  
Purkinje Cells ◽  
Knockout Mice ◽  
Cerebellar Purkinje Cells

Ammonium ions abolish excitatory synaptic transmission between cerebellar neurons in primary dissociated tissue culture

1992 ◽  
Vol 68 (1) ◽  
pp. 93-99 ◽  
Author(s):  
W. Raabe
Keyword(s):  
Tissue Culture ◽  
Synaptic Transmission ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Granule Cells ◽  
Conduction Block ◽  
Excitatory Synaptic Transmission ◽  
Extracellular Solution ◽  
Cell Soma ◽  
Cerebellar Neurons

1. Transmitter glutamate is thought to be derived from glutamine via cleavage by glutaminase. NH+4 inhibits glutaminase. Therefore the decrease of glutamatergic excitatory synaptic transmission by NH+4 was thought to be due to the inability of glutamine to serve as precursor for glutamate. However, in cat spinal cord, NH+4 abolished excitatory synaptic transmission by a conduction block for action potentials in presynaptic terminals. The conduction block prevented inferences as to the effects of NH+4 on the availability of glutamate for synaptic transmission. This study reexamines the effects of NH+4 on glutamatergic excitatory synaptic transmission in cerebellar neurons in tissue culture. 2. Whole-cell patch voltage-clamp recordings were obtained from presumed Purkinje cells. Extracellular stimulation of presumed granule cells produced mono- and polysynaptic excitatory postsynaptic currents (EPSCs). In addition, presumed Purkinje cells showed spontaneous EPSCs that occurred independently of the addition of tetrodotoxin (TTX) or Cd2+ to the extracellular solution. 3. NH+4 (5–10 mM) abolished evoked mono- and polysynaptic EPSCs without abolishing spontaneous EPSCs and without significant effects on action currents in the Purkinje cell soma. 4. Increase of K+ in the extracellular solution to 10-12 from 5 mM abolished evoked EPSCs without abolishing spontaneous EPSCs and without significant effects on action currents in the Purkinje cell soma. 5. Mixtures of NH+4 and K+, with each ion in a concentration insufficient to affect evoked EPSCs when given alone, abolished evoked EPSCs when the sum of NH+4 and K+ exceeded 10–12 mM. 6. Increase of intracellular pH by trimethylamine had no effect on evoked and spontaneous EPSCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous bioelectric activity of cultured cerebellar Purkinje cells during exposure to agents which prevent synaptic transmission

1973 ◽  
Vol 53 (1) ◽  
pp. 71-79 ◽  
Author(s):  
B.H. Ga¨hwiler ◽  
A.M. Mamoon ◽  
C.A. Tobias
Keyword(s):  
Synaptic Transmission ◽  
Purkinje Cells ◽  
Bioelectric Activity ◽  
Cerebellar Purkinje Cells
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