scholarly journals Neuromodulation of astrocytic K+ clearance

2019 ◽  
Author(s):  
Alba Bellot-Saez ◽  
Orsolya Kékesi ◽  
Yuval Ben-Abu ◽  
John W. Morley ◽  
Yossi Buskila
Keyword(s):  
Network Activity ◽  
Oscillatory Behaviour ◽  
Kir Channels ◽  
Neuronal Network Activity ◽  
Synergistic Mechanism ◽  
Synchronous Network ◽  
Clearance Process ◽  
Spatial Buffering ◽  
Parallel Activation ◽  
The Impact

ABSTRACTPotassium homeostasis is a fundamental requirement for normal brain function. Therefore, effective removal of excessive K+ accumulation from the synaptic cleft during neuronal activity is paramount. Astrocytes, one of the most common subtype of glial cells in the brain, play a key role in K+ clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]°) or impairments of the astrocytic clearance mechanism effect the resonance and oscillatory behaviour of both individual and networks of neurons recorded from C57/BL6 mice of both sexes. These results indicate that astrocytes have the potential to modulate neuronal network activity, however the cellular effectors that may affect the astrocytic K+ clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behaviour, on the astrocytic clearance process. Our results suggest that some neuromodulators (5-HT; NA) affect astrocytic spatial buffering via gap-junctions, while others (DA; Histamine) affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to recruitment of neurons into ensamble of networks to maximise the synchronous network activity.Significance statementNeuromodulators are known to mediate changes in network oscillatory behaviour and thus impact on brain states. In this study we show that certain neuromodulators directly affect distinct stages of astrocytic K+ clearance, promoting neuronal excitability and network oscillations through parallel activation of both neurons and astrocytes, thus establishing a synergistic mechanism to maximise the synchronous network activity.

scholarly journals Neuromodulation of Astrocytic K+ Clearance

2021 ◽  
Vol 22 (5) ◽  
pp. 2520
Author(s):  
Alba Bellot-Saez ◽  
Rebecca Stevenson ◽  
Orsolya Kékesi ◽  
Evgeniia Samokhina ◽  
Yuval Ben-Abu ◽  
...  
Keyword(s):  
Oscillatory Behavior ◽  
Network Activity ◽  
Oscillatory Activity ◽  
Extracellular Potassium ◽  
Uptake Mechanism ◽  
Kir Channels ◽  
Neuronal Network Activity ◽  
Clearance Process ◽  
Spatial Buffering ◽  
The Impact

Potassium homeostasis is fundamental for brain function. Therefore, effective removal of excessive K+ from the synaptic cleft during neuronal activity is paramount. Astrocytes play a key role in K+ clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]o) or impairments of the astrocytic clearance mechanism affect the resonance and oscillatory behavior of both the individual and networks of neurons. These results indicate that astrocytes have the potential to modulate neuronal network activity, however, the cellular effectors that may affect the astrocytic K+ clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behavior, on the astrocytic clearance process. Our results suggest that while some neuromodulators (5-HT; NA) might affect astrocytic spatial buffering via gap-junctions, others (DA; Histamine) primarily affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to maximize the synchronous network activity.

scholarly journals The Pentapeptide QYNAD Does Not Inhibit Neuronal Network Activity

2005 ◽  
Vol 32 (3) ◽  
pp. 344-348 ◽  
Author(s):  
F. Otto ◽  
B.C. Kieseier ◽  
P. Görtz ◽  
H.-P. Hartung ◽  
M. Siebler
Keyword(s):  
Sodium Channel ◽  
Neuronal Network ◽  
Single Cells ◽  
Network Activity ◽  
Channel Blockers ◽  
Sodium Currents ◽  
Electrode Arrays ◽  
Sodium Channel Blockers ◽  
Neuronal Network Activity ◽  
The Impact

ABSTRACT:Background:Controversial data was published about the sodium channel-blocking effect of the endogenous pentapeptide QYNAD, which is elevated in patients with multiple sclerosis and Guillain-Barré-syndrome. In some experiments with single cells and nerve preparations QYNAD inhibited sodium currents to the same extent as the known sodium channel blocker lidocaine whereas in other laboratory testing QYNAD failed to show any effect at all.Methods:Micro-electrode arrays with cultured neuronal networks are highly suitable to determine neuroactive activity of applied substances. The impact on electrophysiological parameter changes was compared between QYNAD and the established sodium channel blockers lidocaine and tetrodotoxin (TTX).Results:QYNAD did not alter network activity whereas the sodium channel blockers lidocaine (IC50 14.9 µM) and tetrodotoxin (IC50 1.1 nM) reversibly decreased network activity in similar concentrations as in patch-clamp experiments. This decrease of spontaneous electrophysiological activity was achieved by prolonging the interburst-interval.Conclusion:Although QYNAD might have mild effects on single-cell sodium currents, there is no significant effect on neuronal network function. These results raise concerns about QYNAD exhibiting a relevant impact on functional disability of the central nervous system in patients.

Interactions between network synchrony and the dynamics of neuronal threshold

2012 ◽  
Vol 107 (11) ◽  
pp. 2926-2936 ◽  
Author(s):  
Avner Wallach ◽  
Shimon Marom
Keyword(s):  
Single Neuron ◽  
Cellular Level ◽  
Network Activity ◽  
Threshold Dynamics ◽  
Synchronous Activity ◽  
Interactive Nature ◽  
Synchronous Network ◽  
Health And Disease ◽  
The Impact

Synchronous activity impacts on a range of functional brain capacities in health and disease. To address the interrelations between cellular level activity and network-wide synchronous events, we implemented in vitro a recently introduced technique, the response clamp, which enables online monitoring of single neuron threshold dynamics while ongoing network synchronous activity continues uninterrupted. We show that the occurrence of a synchronous network event causes a significant biphasic change in the single neuron threshold. These threshold dynamics are correlated across the neurons constituting the network and are entailed by the input to the neurons rather than by their own spiking (i.e., output) activity. The magnitude of network activity during a synchronous event is correlated with the threshold state of individual neurons at the event's onset. Recovery from the impact of a given synchronous event on the neuronal threshold lasts several seconds and seems to be a key determinant of the time to the next spontaneously occurring synchronous event. Moreover, the neuronal threshold is shown to be correlated with the excitability dynamics of the entire network. We conclude that the relations between the two levels (network activity and the single neuron threshold) should be thought of in terms that emphasize their interactive nature.

Desynchronisation of neuronal network activity in traumatic brain injury

2008 ◽  
Vol 39 (01) ◽  
Author(s):  
F Otto ◽  
J Opatz ◽  
R Hartmann ◽  
D Willbold ◽  
E Donauer ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Network ◽  
Network Activity ◽  
Neuronal Network Activity

Dementia with Lewy bodies—associated ß-synuclein mutations V70M and P123H cause mutation-specific neuropathological lesions

2021 ◽  
Author(s):  
Maryna Psol ◽  
Sofia Guerin Darvas ◽  
Kristian Leite ◽  
Sameehan U Mahajani ◽  
Mathias Bähr ◽  
...  
Keyword(s):  
Neuronal Network ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Sporadic Case ◽  
Network Activity ◽  
Proteinase K ◽  
Neuronal Network Activity ◽  
Distinct Disease

Abstract ß-Synuclein (ß-Syn) has long been considered to be an attenuator for the neuropathological effects caused by the Parkinson’s disease-related α-Synuclein (α-Syn) protein. However, recent studies demonstrated that overabundant ß-Syn can form aggregates and induce neurodegeneration in CNS neurons in vitro and in vivo, albeit at a slower pace as compared to α-Syn. Here we demonstrate that ß-Syn mutants V70M, detected in a sporadic case of Dementia with Lewy Bodies (DLB), and P123H, detected in a familial case of DLB, robustly aggravate the neurotoxic potential of ß-Syn. Intriguingly, the two mutations trigger mutually exclusive pathways. ß-Syn V70M enhances morphological mitochondrial deterioration and degeneration of dopaminergic and non-dopaminergic neurons, but has no influence on neuronal network activity. Conversely, ß-Syn P123H silences neuronal network activity, but does not aggravate neurodegeneration. ß-Syn WT, V70M and P123H formed proteinase K (PK) resistant intracellular fibrils within neurons, albeit with less stable C-termini as compared to α-Syn. Under cell free conditions, ß-Syn V70M demonstrated a much slower pace of fibril formation as compared to WT ß-Syn, and P123H fibrils present with a unique phenotype characterized by large numbers of short, truncated fibrils. Thus, it is possible that V70M and P123H cause structural alterations in ß-Syn, that are linked to their distinct neuropathological profiles. The extent of the lesions caused by these neuropathological profiles is almost identical to that of overabundant α-Syn, and thus likely to be directly involved into etiology of DLB. Over all, this study provides insights into distinct disease mechanisms caused by mutations of ß-Syn.

Effect of Common Anesthetics on Dendritic Properties in Layer 5 Neocortical Pyramidal Neurons

2008 ◽  
Vol 99 (3) ◽  
pp. 1394-1407 ◽  
Author(s):  
Sarah Potez ◽  
Matthew E. Larkum
Keyword(s):  
High Frequency ◽  
Pyramidal Neurons ◽  
Animal Experiments ◽  
Apical Dendrite ◽  
Network Activity ◽  
Calcium Spikes ◽  
Firing Properties ◽  
The Impact

Understanding the impact of active dendritic properties on network activity in vivo has so far been restricted to studies in anesthetized animals. However, to date no study has been made to determine the direct effect of the anesthetics themselves on dendritic properties. Here, we investigated the effects of three types of anesthetics commonly used for animal experiments (urethane, pentobarbital and ketamine/xylazine). We investigated the generation of calcium spikes, the propagation of action potentials (APs) along the apical dendrite and the somatic firing properties in the presence of anesthetics in vitro using dual somatodendritic whole cell recordings. Calcium spikes were evoked with dendritic current injection and high-frequency trains of APs at the soma. Surprisingly, we found that the direct actions of anesthetics on calcium spikes were very different. Two anesthetics (urethane and pentobarbital) suppressed dendritic calcium spikes in vitro, whereas a mixture of ketamine and xylazine enhanced them. Propagation of spikes along the dendrite was not significantly affected by any of the anesthetics but there were various changes in somatic firing properties that were highly dependent on the anesthetic. Last, we examined the effects of anesthetics on calcium spike initiation and duration in vivo using high-frequency trains of APs generated at the cell body. We found the same anesthetic-dependent direct effects in addition to an overall reduction in dendritic excitability in anesthetized rats with all three anesthetics compared with the slice preparation.

scholarly journals Mining the Virgin Land of Neurotoxicology: A Novel Paradigm of Neurotoxic Peptides Action on Glycosylated Voltage-Gated Sodium Channels

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Zhirui Liu ◽  
Jie Tao ◽  
Pin Ye ◽  
Yonghua Ji
Keyword(s):  
Sodium Channels ◽  
Network Activity ◽  
Voltage Gated ◽  
Virgin Land ◽  
Neuronal Network Activity ◽  
Voltage Gated Sodium Channels ◽  
Pharmacological Targets ◽  
Underlying Mechanisms ◽  
Posttranslation Modification

Voltage-gated sodium channels (VGSCs) are important membrane protein carrying on the molecular basis for action potentials (AP) in neuronal firings. Even though the structure-function studies were the most pursued spots, the posttranslation modification processes, such as glycosylation, phosphorylation, and alternative splicing associating with channel functions captured less eyesights. The accumulative research suggested an interaction between the sialic acids chains and ion-permeable pores, giving rise to subtle but significant impacts on channel gating. Sodium channel-specific neurotoxic toxins, a family of long-chain polypeptides originated from venomous animals, are found to potentially share the binding sites adjacent to glycosylated region on VGSCs. Thus, an interaction between toxin and glycosylated VGSC might hopefully join the campaign to approach the role of glycosylation in modulating VGSCs-involved neuronal network activity. This paper will cover the state-of-the-art advances of researches on glycosylation-mediated VGSCs function and the possible underlying mechanisms of interactions between toxin and glycosylated VGSCs, which may therefore, fulfill the knowledge in identifying the pharmacological targets and therapeutic values of VGSCs.

scholarly journals Neuronal and Astrocytic Regulations in Schizophrenia: A Computational Modelling Study

2021 ◽  
Vol 15 ◽  
Author(s):  
Lea Fritschi ◽  
Johanna Hedlund Lindmar ◽  
Florian Scheidl ◽  
Kerstin Lenk
Keyword(s):  
Computational Models ◽  
Glutamate Release ◽  
Signal Transmission ◽  
Computational Modelling ◽  
Atp Release ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Neuronal Network Activity ◽  
Cell Densities ◽  
Synapse Model

According to the tripartite synapse model, astrocytes have a modulatory effect on neuronal signal transmission. More recently, astrocyte malfunction has been associated with psychiatric diseases such as schizophrenia. Several hypotheses have been proposed on the pathological mechanisms of astrocytes in schizophrenia. For example, post-mortem examinations have revealed a reduced astrocytic density in patients with schizophrenia. Another hypothesis suggests that disease symptoms are linked to an abnormality of glutamate transmission, which is also regulated by astrocytes (glutamate hypothesis of schizophrenia). Electrophysiological findings indicate a dispute over whether the disorder causes an increase or a decrease in neuronal and astrocytic activity. Moreover, there is no consensus as to which molecular pathways and network mechanisms are altered in schizophrenia. Computational models can aid the process in finding the underlying pathological malfunctions. The effect of astrocytes on the activity of neuron-astrocyte networks has been analysed with computational models. These can reproduce experimentally observed phenomena, such as astrocytic modulation of spike and burst signalling in neuron-astrocyte networks. Using an established computational neuron-astrocyte network model, we simulate experimental data of healthy and pathological networks by using different neuronal and astrocytic parameter configurations. In our simulations, the reduction of neuronal or astrocytic cell densities yields decreased glutamate levels and a statistically significant reduction in the network activity. Amplifications of the astrocytic ATP release toward postsynaptic terminals also reduced the network activity and resulted in temporarily increased glutamate levels. In contrast, reducing either the glutamate release or re-uptake in astrocytes resulted in higher network activities. Similarly, an increase in synaptic weights of excitatory or inhibitory neurons raises the excitability of individual cells and elevates the activation level of the network. To conclude, our simulations suggest that the impairment of both neurons and astrocytes disturbs the neuronal network activity in schizophrenia.

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