Increasing Extracellular Potassium Results in Subthalamic Neuron Activity Resembling That Seen in a 6-Hydroxydopamine Lesion

Strauß, Ulf; Zhou, Fu-Wen; Henning, Jeannette; Battefeld, Arne; Wree, Andreas; Köhling, Rüdiger; Haas, Stefan; Rolfs, Arndt; Gimsa, Ulrike

doi:10.1152/jn.00402.2007

Cited by 13 publications

(19 citation statements)

References 66 publications

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“…2b). The occurrence of regular spiking due to an increase of [K] o through diffusion from the bath is consistent with experiments (El Houssaini et al, 2015;Strauss et al, 2008).…”

Section: Resting States Spike Train and Tonic Spiking In Low [K] Bathsupporting

confidence: 88%

A unified physiological framework of transitions between seizures, sustained ictal activity and depolarization block at the single neuron level

et al. 2022

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The majority of seizures recorded in humans and experimental animal models can be described by a generic phenomenological mathematical model, the Epileptor. In this model, seizure-like events (SLEs) are driven by a slow variable and occur via saddle node (SN) and homoclinic bifurcations at seizure onset and offset, respectively. Here we investigated SLEs at the single cell level using a biophysically relevant neuron model including a slow/fast system of four equations. The two equations for the slow subsystem describe ion concentration variations and the two equations of the fast subsystem delineate the electrophysiological activities of the neuron. Using extracellular K+ as a slow variable, we report that SLEs with SN/homoclinic bifurcations can readily occur at the single cell level when extracellular K+ reaches a critical value. In patients and experimental models, seizures can also evolve into sustained ictal activity (SIA) and depolarization block (DB), activities which are also parts of the dynamic repertoire of the Epileptor. Increasing extracellular concentration of K+ in the model to values found during experimental status epilepticus and DB, we show that SIA and DB can also occur at the single cell level. Thus, seizures, SIA, and DB, which have been first identified as network events, can exist in a unified framework of a biophysical model at the single neuron level and exhibit similar dynamics as observed in the Epileptor.Author Summary: Epilepsy is a neurological disorder characterized by the occurrence of seizures. Seizures have been characterized in patients in experimental models at both macroscopic and microscopic scales using electrophysiological recordings. Experimental works allowed the establishment of a detailed taxonomy of seizures, which can be described by mathematical models. We can distinguish two main types of models. Phenomenological (generic) models have few parameters and variables and permit detailed dynamical studies often capturing a majority of activities observed in experimental conditions. But they also have abstract parameters, making biological interpretation difficult. Biophysical models, on the other hand, use a large number of variables and parameters due to the complexity of the biological systems they represent. Because of the multiplicity of solutions, it is difficult to extract general dynamical rules. In the present work, we integrate both approaches and reduce a detailed biophysical model to sufficiently low-dimensional equations, and thus maintaining the advantages of a generic model. We propose, at the single cell level, a unified framework of different pathological activities that are seizures, depolarization block, and sustained ictal activity.

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“…2b). The occurrence of regular spiking due to an increase of [K] o through diffusion from the bath is consistent with experiments (El Houssaini et al, 2015;Strauss et al, 2008).…”

Section: Resting States Spike Train and Tonic Spiking In Low [K] Bathsupporting

confidence: 88%

A unified physiological framework of transitions between seizures, sustained ictal activity and depolarization block at the single neuron level

et al. 2022

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“…Table II gives the details of the equations for each gating variable. For dendrite compartments, there are two passive currents given by accumulation in the interstitial volume [20], We adopt this buffering scheme, which is given by (8) where rt = ffo l + e x p ( i m t ) ' (9) There are only two types of couplings in our model, i.e., the electrical coupling and the potassium diffusive coupling. Because the neurons are modeled in zero-calcium conditions, chemical synapses are neglected.…”

Section: Formalismmentioning

confidence: 99%

“…The extracellular potassium accumulation during neuronal firing was observed by Frankenhaeuser and Hodgkin in 1956 [5], It has been suggested that a direct application of a high potassium solution could induce hippocampal epileptic activity [6], and epileptiform burst discharges could exhibit different patterns due to the variation of background extracellular potassium concentrations [7,8]. Epilepsy has also been shown to be connected with a reduction of the Na+-K+ pump [9] and impairment of the glial K+ uptake [10].…”

Section: Introductionmentioning

confidence: 99%

Effects of extracellular potassium diffusion on electrically coupled neuron networks

Shuai

2015

Phys. Rev. E

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Potassium accumulation and diffusion during neuronal epileptiform activity have been observed experimentally, and potassium lateral diffusion has been suggested to play an important role in nonsynaptic neuron networks. We adopt a hippocampal CA1 pyramidal neuron network in a zero-calcium condition to better understand the influence of extracellular potassium dynamics on the stimulus-induced activity. The potassium concentration in the interstitial space for each neuron is regulated by potassium currents, Na(+)-K(+) pumps, glial buffering, and ion diffusion. In addition to potassium diffusion, nearby neurons are also coupled through gap junctions. Our results reveal that the latency of the first spike responding to stimulus monotonically decreases with increasing gap-junction conductance but is insensitive to potassium diffusive coupling. The duration of network oscillations shows a bell-like shape with increasing potassium diffusive coupling at weak gap-junction coupling. For modest electrical coupling, there is an optimal K(+) diffusion strength, at which the flow of potassium ions among the network neurons appropriately modulates interstitial potassium concentrations in a degree that provides the most favorable environment for the generation and continuance of the action potential waves in the network.

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“…In particular, the persistent Na + current ( I NaP ) is fully blocked, the Ca 2+ -mediated responses are strongly reduced, suggesting a T- and L-type Ca 2+ current depression, whereas the hyperpolarization-activated cationic current ( I h ) is not affected [73]. However, DBS may hyperpolarize local neuronal cell bodies and dendrites directly [37, 72] or indirectly, given the elevated extracellular K+ levels in experimental Parkinsonism [74], which might interfere with normal activity and generate abnormal activity in neural networks [75]. Second, DBS may elicit indirect effects by activating axon terminals that make synaptic connections with neurons near the stimulating electrode (synaptic inhibition).…”

Section: Effects Of Experimental Dbs On Neuronal Activitymentioning

confidence: 99%

Optimizing a Rodent Model of Parkinson's Disease for Exploring the Effects and Mechanisms of Deep Brain Stimulation

Nowak

Mix

Gimsa

et al. 2011

Parkinson's Disease

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Deep brain stimulation (DBS) has become a treatment for a growing number of neurological and psychiatric disorders, especially for therapy-refractory Parkinson's disease (PD). However, not all of the symptoms of PD are sufficiently improved in all patients, and side effects may occur. Further progress depends on a deeper insight into the mechanisms of action of DBS in the context of disturbed brain circuits. For this, optimized animal models have to be developed. We review not only charge transfer mechanisms at the electrode/tissue interface and strategies to increase the stimulation's energy-efficiency but also the electrochemical, electrophysiological, biochemical and functional effects of DBS. We introduce a hemi-Parkinsonian rat model for long-term experiments with chronically instrumented rats carrying a backpack stimulator and implanted platinum/iridium electrodes. This model is suitable for (1) elucidating the electrochemical processes at the electrode/tissue interface, (2) analyzing the molecular, cellular and behavioral stimulation effects, (3) testing new target regions for DBS, (4) screening for potential neuroprotective DBS effects, and (5) improving the efficacy and safety of the method. An outlook is given on further developments of experimental DBS, including the use of transgenic animals and the testing of closed-loop systems for the direct on-demand application of electric stimulation.

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Increasing Extracellular Potassium Results in Subthalamic Neuron Activity Resembling That Seen in a 6-Hydroxydopamine Lesion

Cited by 13 publications

References 66 publications

A unified physiological framework of transitions between seizures, sustained ictal activity and depolarization block at the single neuron level

A unified physiological framework of transitions between seizures, sustained ictal activity and depolarization block at the single neuron level

Effects of extracellular potassium diffusion on electrically coupled neuron networks

Optimizing a Rodent Model of Parkinson's Disease for Exploring the Effects and Mechanisms of Deep Brain Stimulation

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