scholarly journals Tonic Activation of Extrasynaptic NMDA Receptors Decreases Intrinsic Excitability and Promotes Bistability in a Model of Neuronal Activity

2019 ◽  
Vol 21 (1) ◽  
pp. 206
Author(s):  
David Gall ◽  
Geneviève Dupont
Keyword(s):  
Potassium Channels ◽  
Electrical Activity ◽  
Nmda Receptors ◽  
Neuronal Activity ◽  
Neuronal Excitability ◽  
Calcium Influx ◽  
Tonic Activity ◽  
Stimulus Interval ◽  
Simple Description ◽  
Calcium Activated Potassium Channels

NMDA receptors (NMDA-R) typically contribute to excitatory synaptic transmission in the central nervous system. While calcium influx through NMDA-R plays a critical role in synaptic plasticity, experimental evidence indicates that NMDAR-mediated calcium influx also modifies neuronal excitability through the activation of calcium-activated potassium channels. This mechanism has not yet been studied theoretically. Our theoretical model provides a simple description of neuronal electrical activity that takes into account the tonic activity of extrasynaptic NMDA receptors and a cytosolic calcium compartment. We show that calcium influx mediated by the tonic activity of NMDA-R can be coupled directly to the activation of calcium-activated potassium channels, resulting in an overall inhibitory effect on neuronal excitability. Furthermore, the presence of tonic NMDA-R activity promotes bistability in electrical activity by dramatically increasing the stimulus interval where both a stable steady state and repetitive firing can coexist. These results could provide an intrinsic mechanism for the constitution of memory traces in neuronal circuits. They also shed light on the way by which β -amyloids can alter neuronal activity when interfering with NMDA-R in Alzheimer’s disease and cerebral ischemia.

scholarly journals THE EFFECT OF THROMBIN IN THE SERUM-ADAPTED IONIC ENVIRONMENT ON THE INDUCTION OF EPILEPTIFORM FIRING ACTIVITY OF HIPPOCAMPAL CULTURED NEURONS

2021 ◽  
Vol 67 (5) ◽  
pp. 3-10
Author(s):  
M.S. Shypshyna ◽  
◽  
A.V. Savotchenko ◽  
K.I. Kuznetsov ◽  
M.S. Veselovsky ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Epileptiform Activity ◽  
Tonic Activity ◽  
Firing Activity ◽  
Ionic Solution ◽  
Ionic Environment ◽  
Current Clamp Mode ◽  
Glutamate Nmda Receptors

The mechanisms of epileptiform neuronal activity develop- ment under blood-brain barrier (BBB) dysfunction remains relevant in modern psychoneurology. In the present work we mimic some effects of BBB disruption in the culture of hip- pocampal neurons to examined the effect of serum-adapted ionic environment on the impulse activity of hippocampal neurons and the role of serum protein thrombin in induction of epileptiform neuronal activity. Using the whole-cell patch- clamp method under current-clamp mode we analyzed the spontaneous action potentials (AP) in the single hippocampal neurons. The changing of ionic extracellular neuronal environ- ment to such serum-adapted contributed to the development of epileptiform tonic activity of cultured hippocampal neurons and led to increase the average APs frequency by 65.1 ± 17.9% (n = 5) in neurons with spontaneous firing activity (FA) and to occurrence of tonic electrical activity (1.65 ± 0.4 s-1) in neurons without firing activity. Glutamate NMDA receptors significantly contribute to epileptiform tonic activity formation in neurons with FA, while their role in tonic activity providing in neurons without FA was insignificant. Thrombin (5 U/ml) in the serum-adapted ionic solution significantly enhanced of epileptiform activity in neurons with and without spontaneous FA: APs frequency increased in these neuronal groups by 117.3 ± 25.6% (n = 3) and by 61.8 ± 11.5% (n = 3), respective- ly, compared with that in the serum-adapted ionic solution only. Blockade of thrombin protease activated receptor 1 (PAR-1) by application of SCH 79797 (10 μm) canceled the thrombin’s effect in neurons without spontaneous FA, and significantly reduced such in neurons with FA. Therefore, the change of ionic extracellular neuronal environment to serum-adapted stimulates the occurrence of epileptiform activity in hippo- campal neurons, that is apparently associated with NMDA- receptors activation in neurons with FA. The proepileptiform action of thrombin was mostly mediated by PAR-1 activation. Thrombin-dependent regulation of the hippocampal single neurons firing activity involves the mechanisms different from the modulation of glutamate NMDA receptors in these cells.

scholarly journals Potassium channels contribute to activity-dependent scaling of dendritic inhibition

2017 ◽  
Author(s):  
Jeremy T. Chang ◽  
Michael J. Higley
Keyword(s):  
Potassium Channels ◽  
Neuronal Activity ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Gabaergic Inhibition ◽  
Voltage Gated ◽  
The Impact ◽  
Activity Dependent

AbstractGABAergic inhibition plays a critical role in the regulation of neuronal activity. In the neocortex, inhibitory interneurons that target the dendrites of pyramidal cells influence both electrical and biochemical postsynaptic signaling. Voltage-gated ion channels strongly shape dendritic excitability and the integration of excitatory inputs, but their contribution to GABAergic signaling is less well understood. By combining 2-photon calcium imaging and focal GABA uncaging, we show that voltage-gated potassium channels normally suppress the GABAergic inhibition of calcium signals evoked by back-propagating action potentials in dendritic spines and shafts of cortical pyramidal neurons. Moreover, the voltage-dependent inactivation of these channels leads to enhancement of dendritic calcium inhibition following somatic spiking. Computational modeling reveals that the enhancement of calcium inhibition involves an increase in action potential depolarization coupled with the nonlinear relationship between membrane voltage and calcium channel activation. Overall, our findings highlight the interaction between intrinsic and synaptic properties and reveal a novel mechanism for the activity-dependent scaling of GABAergic inhibition.Significance StatementGABAergic inhibition potently regulates neuronal activity in the neocortex. How such inhibition interacts with the intrinsic electrophysiological properties of single neurons is not well-understood. Here we investigate the ability of voltage-gated potassium channels to regulate the impact of GABAergic inhibition in the dendrites of neocortical pyramidal neurons. Our results show that potassium channels normally reduce inhibition directed towards pyramidal neuron dendrites. However, these channels are inactivated by strong neuronal activity, leading to an enhancement of GABAergic potency and limiting the corresponding influx of dendritic calcium. Our findings illustrate a previously unappreciated relationship between neuronal excitability and GABAergic inhibition.

scholarly journals Nitric Oxide Regulates Neuronal Activity via Calcium-Activated Potassium Channels

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e78727 ◽  
Author(s):  
Lei Ray Zhong ◽  
Stephen Estes ◽  
Liana Artinian ◽  
Vincent Rehder
Keyword(s):  
Nitric Oxide ◽  
Potassium Channels ◽  
Neuronal Activity ◽  
Calcium Activated Potassium Channels

Immediate diaphragmatic electromyogram responses to imperceptible mechanical loads in conscious humans

1992 ◽  
Vol 73 (1) ◽  
pp. 248-259 ◽  
Author(s):  
E. J. Kobylarz ◽  
J. A. Daubenspeck
Keyword(s):  
Electrical Activity ◽  
Lung Volume ◽  
Muscle Activity ◽  
Normal Subjects ◽  
Tonic Activity ◽  
Phasic Activity ◽  
Mechanical Loads ◽  
Oral Airway ◽  
Pattern Regulation ◽  
Adaptive Pattern

We used an esophageal electrode to measure the amplitude and neural inspiratory and expiratory (N TE) timing responses of crural diaphragmatic electrical activity in response to flow-resistive (R) and elastic (E) loads at or below the threshold for conscious detection, applied pseudorandomly to the oral airway of eight normal subjects. We observed a rapid first-breath neural reflex that modified respiratory timing such that N TE lengthened significantly in response to R loads in six of eight subjects and shortened in response to E loading in six of seven subjects. The prolongation of N TE with R loading resulted primarily from lengthening the portion of N TE during which phasic activity in the diaphragm is absent (TE NDIA), whereas E loading shortened N TE mainly by reducing TE NDIA. Most subjects responded to both types of loading by decreasing mean tonic diaphragmatic activity, the average level of muscle activity that exists when no phasic changes are occurring, as well as its variability. The observed timing responses are consistent in direction with optimally adaptive pattern regulation, whereas the modulation of tonic activity may be useful in neural regulation of end-expiratory lung volume.

[125I]Iberiotoxin-D19Y/Y36F, the First Selective, High Specific Activity Radioligand for High-Conductance Calcium-Activated Potassium Channels

Biochemistry ◽  
1997 ◽  
Vol 36 (7) ◽  
pp. 1943-1952 ◽  
Author(s):  
Alexandra Koschak ◽  
Robert O. Koch ◽  
Jessica Liu ◽  
Gregory J. Kaczorowski ◽  
Peter H. Reinhart ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Specific Activity ◽  
High Specific Activity ◽  
Calcium Activated Potassium Channels ◽  
High Conductance
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