Changes in neuronal excitability and synaptic function in a chronic model of temporal lobe epilepsy

Bernard, Christophe; Marsden, David; Wheal, H.V.

doi:10.1016/s0306-4522(00)00524-8

Cited by 14 publications

(6 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5) with a similar change of steepness of scaling (Andrasfalvy et al 2003). Moreover, similar changes have been reported in the pathophysiological condition of temporal lobe epilepsy (Bernard et al 2001, 2004; Cossart et al 2001; Bernard & Johnston, 2003; Mody, 2005; Glykys & Mody, 2006; El‐Hassar et al 2007), where Kv4.2 expression, I h current and tonic and phasic inhibition are all altered at different stages of epilepsy causing excitability alteration with a concomitant change of distance‐dependent synaptic scaling (Andrásfalvy & Mody, 2005). To better understand the dynamic regulation of synaptic efficacy, further investigation is needed at the right time‐scale of these different forms of synaptic plasticity.…”

Section: Discussionsupporting

confidence: 66%

Altered synaptic and non‐synaptic properties of CA1 pyramidal neurons in Kv4.2 knockout mice

Andrásfalvy

Makara

Johnston

et al. 2008

The Journal of Physiology

View full text Add to dashboard Cite

Back-propagating action potentials (bAPs) travelling from the soma to the dendrites of neurons are involved in various aspects of synaptic plasticity. The distance-dependent increase in Kv4.2-mediated A-type K + current along the apical dendrites of CA1 pyramidal cells (CA1 PCs) is responsible for the attenuation of bAP amplitude with distance from the soma. Genetic deletion of Kv4.2 reduced dendritic A-type K + current and increased the bAP amplitude in distal dendrites. Our previous studies revealed that the amplitude of unitary Schaffer collateral inputs increases with distance from the soma along the apical dendrites of CA1 PCs. We tested the hypothesis that the weight of distal synapses is dependent on dendritic Kv4.2 channels. We compared the amplitude and kinetics of mEPSCs at different locations on the main apical trunk of CA1 PCs from wild-type (WT) and Kv4.2 knockout (KO) mice. While wild-type mice showed normal distance-dependent scaling, it was missing in the Kv4.2 KO mice. We also tested whether there was an increase in inhibition in the Kv4.2 knockout, induced in an attempt to compensate for a non-specific increase in neuronal excitability (after-polarization duration and burst firing probability were increased in KO). Indeed, we found that the magnitude of the tonic GABA current increased in Kv4.2 KO mice by 53% and the amplitude of mIPSCs increased by 25%, as recorded at the soma. Our results suggest important roles for the dendritic K + channels in distance-dependent adjustment of synaptic strength as well as a primary role for tonic inhibition in the regulation of global synaptic strength and membrane excitability.

show abstract

Section: Discussionsupporting

confidence: 66%

Altered synaptic and non‐synaptic properties of CA1 pyramidal neurons in Kv4.2 knockout mice

Andrásfalvy

Makara

Johnston

et al. 2008

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…Taken together, our data argue against coordinated control of independent homeostatic responses. If generalized, these data could influence our view of neurological disease if an initial stress initiates a primary homeostatic response that is restorative, but with consequences for the future capacity of that cell to adapt or respond to additional perturbations (Bernard et al, 2004; Bernard and Johnston, 2003; Bernard et al, 2001; Cossart et al, 2001; El-Hassar et al, 2007; Frohlich et al, 2008; Glykys and Mody, 2006; Mody, 2005). …”

Section: Introductionmentioning

confidence: 99%

A Hierarchy of Cell Intrinsic and Target-Derived Homeostatic Signaling

Bergquist

Dickman

Davis

2010

Neuron

109

View full text Add to dashboard Cite

Homeostatic control of neural function can be mediated by the regulation of ion channel expression, neurotransmitter receptor abundance, or modulation of presynaptic release. These processes can be implemented through cell autonomous or intercellular signaling. It remains unknown whether different forms of homeostatic regulation can be coordinated to achieve constant neural function. One way to approach this question is to confront a simple neural system with conflicting perturbations and determine whether the outcome reflects a coordinated, homeostatic response. Here we demonstrate that two A-type potassium channel genes, shal and shaker, are reciprocally, transcriptionally coupled to maintain A-type channel expression. We then demonstrate that this homeostatic control of A-type channel expression prevents target-dependent, homeostatic modulation of synaptic transmission. Thus, we uncover a novel homeostatic mechanism that reciprocally regulates A-type potassium channels and we define a hierarchical relationship between cell-intrinsic control of ion channel expression and target-derived homeostatic control of synaptic transmission.

show abstract

“…In partial epilepsy, seizures are associated with pathologically increased excitability or synchronization as well as deficient inhibitory control within the epileptic focus (12–14). At the cellular level, the generation of burst discharges depends on the stability of the membrane potential, which is determined by ion (i.e., sodium and calcium) homeostasis.…”

mentioning

confidence: 99%

Anticonvulsant Effects of Transcranial Direct‐current Stimulation (tDCS) in the Rat Cortical Ramp Model of Focal Epilepsy

et al. 2006

View full text Add to dashboard Cite

Summary:Purpose: Weak direct currents induce lasting alterations of cortical excitability in animals and humans, which are controlled by polarity, duration of stimulation, and current strength applied. To evaluate its anticonvulsant potential, transcranial direct current stimulation (tDCS) was tested in a modified cortical ramp-stimulation model of focal epilepsy.Methods: The threshold for localized seizure activity (TLS) was determined in freely moving rats by applying a single train of rising bipolar pulses through a unilateral epicranial electrode. After tDCS, TLS was determined repeatedly for 120 min at intervals of 15 min. The first group of animals received two sessions of cathodal tDCS at 100 μA, one for 30 and one for 60 min. A third session consisted of 60 min of anodal tDCS. A second group received cathodal tDCS at 200 μA for 15 and for 30 min, as well as anodal tDCS for 30 min.Results: Sixty minutes of cathodal tDCS at 100 μA resulted in a TLS increase lasting for ≥2 h. When the intensity was increased to 200 μA, a similar lasting TLS elevation occurred after a stimulation of just 30-min duration. In contrast, anodal tDCS at identical stimulation durations and current strengths had no significant effect on TLS.Conclusions: The anticonvulsive effect induced by cathodal tDCS depends on stimulation duration and current strength and may be associated with the induction of alterations of cortical excitability that outlast the actual stimulation. The results lead to the reasonable assumption that cathodal tDCS could evolve as a therapeutic tool in drug-refractory partial epilepsy.

show abstract

Changes in neuronal excitability and synaptic function in a chronic model of temporal lobe epilepsy

Cited by 14 publications

References 37 publications

Altered synaptic and non‐synaptic properties of CA1 pyramidal neurons in Kv4.2 knockout mice

Altered synaptic and non‐synaptic properties of CA1 pyramidal neurons in Kv4.2 knockout mice

A Hierarchy of Cell Intrinsic and Target-Derived Homeostatic Signaling

Anticonvulsant Effects of Transcranial Direct‐current Stimulation (tDCS) in the Rat Cortical Ramp Model of Focal Epilepsy

Contact Info

Product

Resources

About