Cellular and network mechanisms of electrographic seizures

Bazhenov, Maxim; Timofeev, Igor; Fröhlich, Flavio; Sejnowski, Terrence J.

doi:10.1016/j.ddmod.2008.07.005

Cited by 63 publications

(53 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As an additional mechanism, network driven K 1 accumulation is thought to enhance the depolarizing response by both direct membrane depolarization and a reduction of Cl 2 extrusion (McCarren and Alger, 1985;Kaila et al, 1997;Bazhenov et al, 2008; see note added in proof; see also Perkins and Wong, 1996;Perkins, 1999). Our simulations suggest that under appropriate conditions, the GDPSP may be evoked by tetanic stimulation even if GABAergic activity is not accompanied by extracellular K 1 accumulation.…”

Section: Accumulation and Gabaergic Depolarizationmentioning

confidence: 75%

Activity‐dependent intracellular chloride accumulation and diffusion controls GABA_A receptor‐mediated synaptic transmission

et al. 2011

View full text Add to dashboard Cite

In the CNS, prolonged activation of GABA(A) receptors (GABA(A)Rs) has been shown to evoke biphasic postsynaptic responses, consisting of an initial hyperpolarization followed by a depolarization. A potential mechanism underlying the depolarization is an acute chloride (Cl(-)) accumulation resulting in a shift of the GABA(A) reversal potential (E(GABA)). The amount of GABA-evoked Cl(-) accumulation and accompanying depolarization depends on presynaptic and postsynaptic properties of GABAergic transmission, as well as on cellular morphology and regulation of Cl(-) intracellular concentration ([Cl(-)](i)). To analyze the influence of these factors on the Cl(-) and voltage behavior, we studied spatiotemporal dynamics of activity-dependent [Cl(-)](i) changes in multicompartmental models of hippocampal cells based on realistic morphological data. Simulated Cl(-) influx through GABA(A) Rs was able to exceed physiological Cl(-) extrusion rates thereby evoking HCO(3)(-) -dependent E(GABA) shift and depolarizing responses. Depolarizations were observed in spite of GABA(A) receptor desensitization. The amplitude of the depolarization was frequency-dependent and determined by intracellular Cl(-) accumulation. Changes in the dendritic diameter and in the speed of GABA clearance in the synaptic cleft were significant sources of depolarization variability. In morphologically reconstructed granule cells subjected to an intense GABAergic background activity, dendritic inhibition was more affected by accumulation of intracellular Cl(-) than somatic inhibition. Interestingly, E(GABA) changes induced by activation of a single dendritic synapse propagated beyond the site of Cl(-) influx and affected neighboring synapses. The simulations suggest that E(GABA) may differ even along a single dendrite supporting the idea that it is necessary to assign E(GABA) to a given GABAergic input and not to a given neuron.

show abstract

Section: Accumulation and Gabaergic Depolarizationmentioning

confidence: 75%

Activity‐dependent intracellular chloride accumulation and diffusion controls GABA_A receptor‐mediated synaptic transmission

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The importance of adequate excitability levels is highlighted by the pathological consequences and impaired performance resulting from aberrant network excitability. In epilepsy, changes in cortical network excitability are believed to be an important cause underlying the initiation and spread of seizures, that is, the large nonphysiological neuronal activity events across time and space (1)(2)(3). Evidence for changes of excitability in brain networks affected in epilepsy has come from a variety of observations.…”

mentioning

confidence: 99%

Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle

Meisel

Schulze‐Bonhage

Freestone

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

121

112

View full text Add to dashboard Cite

Pathological changes in excitability of cortical tissue commonly underlie the initiation and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring excitability and controlling its degree using antiepileptic drugs (AEDs) is of prime importance for clinical care and treatment. To date, adequate measures of excitability and action of AEDs have been difficult to identify. Recent insights into ongoing cortical activity have identified global levels of phase synchronization as measures that characterize normal levels of excitability and quantify any deviation therefrom. Here, we explore the usefulness of these intrinsic measures to quantify cortical excitability in humans. First, we observe a correlation of such markers with stimulation-evoked responses suggesting them to be viable excitability measures based on ongoing activity. Second, we report a significant covariation with the level of AED load and a wake-dependent modulation. Our results indicate that excitability in epileptic networks is effectively reduced by AEDs and suggest the proposed markers as useful candidates to quantify excitability in routine clinical conditions overcoming the limitations of electrical or magnetic stimulation. The wake-dependent time course of these metrics suggests a homeostatic role of sleep, to rebalance cortical excitability.excitability | epilepsy | sleep N ormal functioning of cortical networks critically depends on a finely tuned level of excitability, the transient or steady-state response in which the brain reacts to a stimulus. Whereas small, local responses indicate a comparably small excitability, large and global responses consequently suggest excitability to be high. The importance of adequate excitability levels is highlighted by the pathological consequences and impaired performance resulting from aberrant network excitability. In epilepsy, changes in cortical network excitability are believed to be an important cause underlying the initiation and spread of seizures, that is, the large nonphysiological neuronal activity events across time and space (1-3). Evidence for changes of excitability in brain networks affected in epilepsy has come from a variety of observations. To assess the level of excitability under in vivo experimental conditions one usually measures the size of the evoked cortical activity to external perturbations, typically either by transcranial magnetic stimulation (TMS) or, in the case of epilepsy patients, by electrical stimulation. Studies of electrical stimulation with subdural electrodes during interictal periods found the evoked potentials to be larger in regions related to the cortical onset region of epileptiform activity (4-6). The enhanced responses to electrical stimulation in epileptogenic cortex were taken as indication of an increased excitability of neural tissue in these areas. Similarly, studies using TMS consistently reported a hyperexcitability in focal epilepsies (7-10). Consequently, changes in excitability have been helpful in identifying the se...

show abstract

“…The time courses of various inhibitory synaptic processes in the neocortex have been shown to be highly variable and span more than one order of magnitude (Thomson and Deuchars 1997;Otis and De Koninck 1993). However, the origin of the slow timescale resulting from GABA B receptor activation has recently been challenged (Bazhenov et al 2008). It is therefore possible that the slow process might also be attributed to non-synaptic mechanisms which our phenomenological model can also account for.…”

Section: Discussionmentioning

confidence: 96%

A spatially extended model for macroscopic spike-wave discharges

Taylor

Baier

2011

J Comput Neurosci

View full text Add to dashboard Cite

Spike-wave discharges are a distinctive feature of epileptic seizures. So far, they have not been reported in spatially extended neural field models. We study a space-independent version of the Amari neural field model with two competing inhibitory populations. We show that this competition leads to robust spike-wave dynamics if the inhibitory populations operate on different time-scales. The spike-wave oscillations present a fold/homoclinic type bursting. From this result we predict parameters of the extended Amari system where spike-wave oscillations produce a spatially homogeneous pattern. We propose this mechanism as a prototype of macroscopic epileptic spike-wave discharges. To our knowledge this is the first example of robust spike-wave patterns in a spatially extended neural field model.

show abstract

Cellular and network mechanisms of electrographic seizures

Cited by 63 publications

References 97 publications

Activity‐dependent intracellular chloride accumulation and diffusion controls GABA_A receptor‐mediated synaptic transmission

Activity‐dependent intracellular chloride accumulation and diffusion controls GABA_A receptor‐mediated synaptic transmission

Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle

A spatially extended model for macroscopic spike-wave discharges

Contact Info

Product

Resources

About

Cellular and network mechanisms of electrographic seizures

Cited by 63 publications

References 97 publications

Activity‐dependent intracellular chloride accumulation and diffusion controls GABAA receptor‐mediated synaptic transmission

Activity‐dependent intracellular chloride accumulation and diffusion controls GABAA receptor‐mediated synaptic transmission

Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle

A spatially extended model for macroscopic spike-wave discharges

Contact Info

Product

Resources

About

Activity‐dependent intracellular chloride accumulation and diffusion controls GABA_A receptor‐mediated synaptic transmission

Activity‐dependent intracellular chloride accumulation and diffusion controls GABA_A receptor‐mediated synaptic transmission