The role of relative membrane capacitance and time delay in cerebellar Purkinje cells

2017 ◽  
Vol 62 (5) ◽  
Author(s):  
Jing Wang ◽  
Shenquan Liu ◽  
Bo Lu ◽  
Yanjun Zeng
Keyword(s):  
Time Delay ◽  
Purkinje Cells ◽  
Compartment Model ◽  
Signal Propagation ◽  
Electrical Signal ◽  
Membrane Capacitance ◽  
Neuronal Firing ◽  
Two Compartment Model ◽  
Cerebellar Purkinje Cells

AbstractThe membrane capacitance of a neuron can influence the synaptic efficacy and the speed of electrical signal propagation. Exploring the role of membrane capacitance will help facilitate a deeper understanding of the electrical properties of neurons. Thus, in this paper, we investigated the neuronal firing behaviors of a two-compartment model in Purkinje cells. We evaluated the influence of membrane capacitance under two different circumstances: in the absence of time delay and in the presence of time delay. Firstly, we separately studied the influence of somatic membrane capacitance

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.

Modulatory role of serotonin on GABA-elicited inhibition of cerebellar Purkinje cells

Neuroscience ◽  
1989 ◽  
Vol 30 (1) ◽  
pp. 117-125 ◽  
Author(s):  
J.C. Strahlendorf ◽  
M. Lee ◽  
H.K. Strahlendorf
Keyword(s):  
Purkinje Cells ◽  
Cerebellar Purkinje Cells

scholarly journals Spike burst–pause dynamics of Purkinje cells regulate sensorimotor adaptation

2018 ◽  
Author(s):  
Niceto R. Luque ◽  
Francisco Naveros ◽  
Richard R. Carrillo ◽  
Eduardo Ros ◽  
Angelo Arleo
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Vestibular Nuclei ◽  
Response Patterns ◽  
Spike Burst ◽  
Vor Adaptation ◽  
Cell Firing ◽  
Cerebellar Purkinje Cells ◽  
Oculomotor Adaptation

AbstractCerebellar Purkinje cells mediate accurate eye movement coordination. However, it remains unclear how oculomotor adaptation depends on the interplay between the characteristic Purkinje cell response patterns, namely tonic, bursting, and spike pauses. Here, a spiking cerebellar model assesses the role of Purkinje cell firing patterns in vestibular ocular reflex (VOR) adaptation. The model captures the cerebellar microcircuit properties and it incorporates spike-based synaptic plasticity at multiple cerebellar sites. A detailed Purkinje cell model reproduces the three spike-firing patterns that are shown to regulate the cerebellar output. Our results suggest that pauses following Purkinje complex spikes (bursts) encode transient disinhibition of targeted medial vestibular nuclei, critically gating the vestibular signals conveyed by mossy fibres. This gating mechanism accounts for early and coarse VOR acquisition, prior to the late reflex consolidation. In addition, properly timed and sized Purkinje cell bursts allow the ratio between long-term depression and potentiation (LTD/LTP) to be finely shaped at mossy fibre-medial vestibular nuclei synapses, which optimises VOR consolidation. Tonic Purkinje cell firing maintains the consolidated VOR through time. Importantly, pauses are crucial to facilitate VOR phase-reversal learning, by reshaping previously learnt synaptic weight distributions. Altogether, these results predict that Purkinje spike burst-pause dynamics are instrumental to VOR learning and reversal adaptation.Author SummaryCerebellar Purkinje cells regulate accurate eye movement coordination. However, it remains unclear how cerebellar-dependent oculomotor adaptation depends on the interplay between Purkinje cell characteristic response patterns: tonic, high-frequency bursting, and post-complex spike pauses. We explore the role of Purkinje spike burst-pause dynamics in VOR adaptation. A biophysical model of Purkinje cell is at the core of a spiking network model, which captures the cerebellar microcircuit properties and incorporates spike-based synaptic plasticity mechanisms at different cerebellar sites. We show that Purkinje spike burst-pause dynamics are critical for (1) gating the vestibular-motor response association during VOR acquisition; (2) mediating the LTD/LTP balance for VOR consolidation; (3) reshaping synaptic efficacy distributions for VOR phase-reversal adaptation; (4) explaining the reversal VOR gain discontinuities during sleeping.

scholarly journals Modulation of Increased mGluR1 Signaling by RGS8 Protects Purkinje Cells From Dendritic Reduction and Could Be a Common Mechanism in Diverse Forms of Spinocerebellar Ataxia

2021 ◽  
Vol 8 ◽  
Author(s):  
Qin-Wei Wu ◽  
Josef P. Kapfhammer
Keyword(s):  
Purkinje Cells ◽  
Spinocerebellar Ataxia ◽  
Common Mechanism ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Spinocerebellar Ataxias ◽  
Negative Effects ◽  
The Moment ◽  
Cerebellar Purkinje Cells

Spinocerebellar ataxias (SCAs) are a group of hereditary neurodegenerative diseases which are caused by diverse genetic mutations in a variety of different genes. We have identified RGS8, a regulator of G-protein signaling, as one of the genes which are dysregulated in different mouse models of SCA (e.g., SCA1, SCA2, SCA7, and SCA14). In the moment, little is known about the role of RGS8 for pathogenesis of spinocerebellar ataxia. We have studied the expression of RGS8 in the cerebellum in more detail and show that it is specifically expressed in mouse cerebellar Purkinje cells. In a mouse model of SCA14 with increased PKCγ activity, RGS8 expression was also increased. RGS8 overexpression could partially counteract the negative effects of DHPG-induced mGluR1 signaling for the expansion of Purkinje cell dendrites. Our results suggest that the increased expression of RGS8 is an important mediator of mGluR1 pathway dysregulation in Purkinje cells. These findings provide new insights in the role of RGS8 and mGluR1 signaling in Purkinje cells and for the pathology of SCAs.

scholarly journals Altered Glutamate Receptor Ionotropic Delta Subunit 2 Expression in Stau2-Deficient Cerebellar Purkinje Cells in the Adult Brain

2019 ◽  
Vol 20 (7) ◽  
pp. 1797 ◽  
Author(s):  
Helena F. Pernice ◽  
Rico Schieweck ◽  
Mehrnoosh Jafari ◽  
Tobias Straub ◽  
Martin Bilban ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Glutamate Receptor ◽  
Rna Binding ◽  
Wheel Running ◽  
Adult Brain ◽  
Learning Abilities ◽  
Cerebellar Purkinje Cells ◽  
And Function ◽  
Delta Subunit

Staufen2 (Stau2) is an RNA-binding protein that is involved in dendritic spine morphogenesis and function. Several studies have recently investigated the role of Stau2 in the regulation of its neuronal target mRNAs, with particular focus on the hippocampus. Here, we provide evidence for Stau2 expression and function in cerebellar Purkinje cells. We show that Stau2 downregulation (Stau2GT) led to an increase of glutamate receptor ionotropic delta subunit 2 (GluD2) in Purkinje cells when animals performed physical activity by voluntary wheel running compared with the age-matched wildtype (WT) mice (C57Bl/6J). Furthermore, Stau2GT mice showed lower performance in motor coordination assays but enhanced motor learning abilities than did WT mice, concomitantly with an increase in dendritic GluD2 expression. Together, our results suggest the novel role of Stau2 in Purkinje cell synaptogenesis in the mouse cerebellum.

Two fluid compartments in the renal inner medulla: a view through the keyhole of the concentrating process

2006 ◽  
Vol 364 (1843) ◽  
pp. 1551-1561 ◽  
Author(s):  
G.G Pinter ◽  
J.L Shohet
Keyword(s):  
Mammalian Species ◽  
Compartment Model ◽  
Plasma Albumin ◽  
Two Compartment Model ◽  
Primary Responsibility ◽  
Renal Inner Medulla ◽  
Fluid Compartments ◽  
New Hypothesis ◽  
Two Fluid

Approximately four decades ago, the countercurrent theory became influential in studies on the concentrating process in the mammalian kidney. The theory successfully represented the concentrating process in the outer medulla, but the problem of the concentrating mechanism in the inner medulla, as defined by Homer Smith has remained essentially intractable. In a recent comprehensive review by Knepper and coworkers of various theories and models, attention was refocused on the possible role of hyaluronate (HA) in the inner medullary concentrating process. The authors proposed a hypothesis that HA can convert hydrostatic pressure to concentrating work. Here, we briefly survey the earlier ideas on the role imputed to HA and present a new hypothesis which is different from that of Knepper and coworkers. We estimate that the hydrostatic pressures available in the inner medulla can account only for a very small fraction of the concentrating work. We hypothesize that the role of HA is tied up with extravasated plasma albumin and suggest that owing to the property of HA solutions to exclude other macromolecules, extravasated plasma albumin and HA constitute two fluid compartments in the interstitium in the inner medulla. In this proposed two-compartment model, the Gibbs-Donnan distribution influences the movement of ions and water between the HA and the extravasated albumin compartment. To relate the hypothetical role of HA to the concentrating process, we briefly describe new results obtained by other investigators on the accumulation of urea in the inner medulla. This subject has been critically reviewed recently by Yang & Bankir. Many processes have been identified as contributing to the concentrating process in the mammalian inner medulla. We speculate that among these many processes, the primary responsibility for the final concentration of the excreted urine may be portioned out differently in different mammalian species.

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