Calcium currents in pyramidal CA1 neurons in vitro after kindling epileptogenesis in the hippocampus of the rat

Faas, Guido C.; Vreugdenhil, Martin; Wadman, W.J.

doi:10.1016/0306-4522(96)00254-0

Cited by 84 publications

(55 citation statements)

References 49 publications

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“…Therefore, the primary utility of drugs effective in these screens would probably be against secondary generalization of seizures. However, it is clear from the studies described above and studies describing alterations in excitatory amino acid receptors (60)(61)(62)77) and other ion channels (64,(78)(79)(80) in focal tissue within the epileptic brain that many ion channels and receptors in these critical epileptogenic sites are fundamentally different from those in control tissue. Future efforts targeting these "epileptic" ion channels may have therapeutic benefit in controlling initiation of seizures rather than seizure spread.…”

Section: "Epileptic" Ion Channels: Implications For Drug Development mentioning

confidence: 94%

Chronic Epileptogenic Cellular Alterations in the Limbic System After Status Epilepticus

Coulter

1999

Epilepsia

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Summary: Status epilepticus (SE) is associated with both acute and permanent pathological sequellae. One common long term consequence of SE is the subsequent development of a chronic epileptic condition, with seizures frequently originating from and involving the limbic system. Following SE, many studies have demonstrated selective loss of neurons within the hilar region of the dentate gyrus, CA1 and CA3 pyramidal neurons. Selective loss of distinct subpopulations of interneurons throughout the hippocampus is also frequently evident, although interneurons as a whole are selectively spared relative to principal cells. Accompanying this loss of neurons are circuit rearrangements, the most widely studied being the sprouting of dentate granule cell (DGC) axons back onto the inner molecular layer of the dentate gyrus, termed mossy fiber sprouting. Less studied are the receptor properties of the surviving neurons within the epileptic hippocampus following SE. DGCs in epileptic animals exhibit marked alterations in the functional and pharmacological properties of y-aminobutyric acid (GABA) receptors. DGCs have a significantly elevated density of GABA, receptors in chronically epileptic animals. In addition, the pharmacological properties of GABA, receptors in Status epilepticus (SE) is a severe and debilitating prolonged seizure that lasts for 30 min or longer and is frequently associated with significant acute mortality as well as long-term morbidity. In addition to the short-term impact of an episode SE on the anatomy and function of the CNS, there are also devastating long-term consequences. One of the most prevalent of these is the subsequent development of a chronic epileptic condition, with seizures frequently originating from and involving the limbic system. This association has been exploited experimentally in the development of animal models of temporal lobe epilepsy (TLE). Several post-SE epileptic animals are quite different compared to controls. In particular, GABA, receptors in DGCs from epileptic animals show an enhanced sensitivity to blockade by zinc, and a markedly altered sensitivity to modulation by benzodiazepines. These pharmacological differences may be due to a decreased expression of a 1 subunits of the GABA, receptor relative to other a subunits in DGCs of post-SE epileptic animals. These GABA, receptor alterations precede the onset of spontaneous seizures in post-SE DGCs, and so are temporally positioned to contribute to the process of epileptogenesis in the limbic system. The presence of zinc sensitive GABA receptors combined with the presence of zinc-containing "sprouted" mossy fiber terminals innervating the proximal dendrites of DGCs in the post-SE epileptic hippocampus prompted the development of the hypothesis that repetitive activation of the DG in the epileptic brain could result in the release of zine. This zinc in turn may diffuse to and block "epileptic" zinc-sensitive GABA, receptors in DGCs, leading to a catastrophic failure of inhibition and concomitant enhanced seizure propens...

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Section: "Epileptic" Ion Channels: Implications For Drug Development mentioning

confidence: 94%

Chronic Epileptogenic Cellular Alterations in the Limbic System After Status Epilepticus

Coulter

1999

Epilepsia

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“…Both increased and decreased activity of HVA Ca 2+ currents have been seen [Faas et al, 1996;Mody et al, 1990]. In several genetic models of epilepsy, the primary defect involved voltage-gated Ca 2+ channels, but the mechanism of epileptogenesis was not clear (Ryan, 1999].…”

Section: Membrane Propertiesmentioning

confidence: 99%

“…T channels are localized to the soma and dendrites of CA1 pyramidal neurons and, thus, well positioned to play an important role in neuronal excitability and synaptic plasticity [Magee et al, 1998]. Increased activity of T-type Ca 2+ currents was present in one model of absence epilepsy [Tsakiridou et al, 1995] and in brain slices from kindled animals [Faas et al, 1996]. The TTX model of epilepsy is one of the first to show the role of an altered Ca 2+ current in the developing brain.…”

Section: Membrane Propertiesmentioning

confidence: 99%

Chronic Epilepsy in Developing Hippocampal Neurons: Electrophysiologic and Morphologic Features

Niesen¹,

Ge²

1999

Dev Neurosci

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Despite the susceptibility of immature neurons to seizures, there are few models of epilepsy in the developing brain. By taking advantage of activity-dependent developmental changes in young neurons, we have developed a novel model of chronic epilepsy in cultured hippocampal slices. Incubating slices in tetrodotoxin (TTX) for at least 1 week produced significant changes in the electrical activity and appearance of CA1 pyramidal neurons. Extracellular recordings revealed multiple population spikes, and, in whole-cell recordings, evoked synaptic potentials lasting hundreds of milliseconds with many superimposed action potentials were present. Spontaneous firing with burst-like discharges was also evident. These changes were secondary to increased AMPA-receptor-mediated responses and decreased GABA_A receptor events. Altered membrane properties involved increased expression of T-type Ca²⁺ channels which are normally down-regulated in these neurons. TTX-treated neurons also showed abnormal dendritic branching. This model of chronic epilepsy in developing hippocampal neurons demonstrated many changes at the membrane, cellular and synaptic level that may provide new insights into the nature of epileptogenesis in the young brain.

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“…Epileptic seizure activity is associated with significant changes in calcium influx, intracellular calcium concentration, and calcium-dependent secondary mechanisms (Heinemann et al 1990;Faas et al 1996). Abraham and Huggett (1997) showed that in the CA1 region of the hippocampus, overstimulation transiently inhibits subsequent LTP induction through activation of voltage-gated calcium channels (VGCCs) and of NMDA receptors.…”

Section: Synaptic Plasticity In Kindled Ratsmentioning

confidence: 99%

Kindling-induced changes in plasticity of the rat amygdala and hippocampus

Schubert¹,

Siegmund²,

Pape³

et al. 2005

Learn. Mem.

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Temporal lobe epilepsy (TLE) is often accompanied by interictal behavioral abnormalities, such as fear and memory impairment. To identify possible underlying substrates, we analyzed long-term synaptic plasticity in two relevant brain regions, the lateral amygdala (LA) and the CA1 region of the hippocampus, in the kindling model of epilepsy. Wistar rats were kindled through daily administration of brief electrical stimulations to the left basolateral nucleus of the amygdala. Field potential recordings were performed in slices obtained from kindled rats 48 h after the last induced seizure, and in slices from sham-implanted and nonimplanted controls. Kindling resulted in a significant impairment of long-term potentiation (LTP) in both the LA and the CA1, the magnitude of which was dependent on the number of prior stage V seizures. Saturation of CA1-LTP, assessed through repeated spaced delivery of high-frequency stimulation, occurred at lower levels in kindled compared to sham-implanted animals, consistent with the hypothesis of reduced capacity of further synaptic strengthening. Furthermore, theta pulse stimulation elicited long-term depression in the amygdala in nonimplanted and sham-implanted controls, whereas the same stimulation protocol stimulation caused LTP in kindled rats. In conclusion, kindling differentially affects the magnitude, saturation, and polarity of LTP in the CA1 and LA, respectively, most likely indicating an activity-dependent mechanism in the context of synaptic metaplasticity.Convulsive diseases in humans such as temporal lobe epilepsy (TLE) are often accompanied by impairments of learning and memory. In addition, TLE patients typically display emotional disturbances, in particular negative emotions such as fear, anxiety, and depression (Kalynchuk 2000). A wealth of data has established that the amygdala plays a critical role in neuronal activity and synaptic plasticity related to both emotionally modulated signal processing and epilepsy (Gloor 1990;Maren 1999;LeDoux 2000). Synapses in the amygdala display long-term potentiation (LTP) (Chapman and Chattarji 2000; LeDoux 2000; Maren 2001), a long-lasting increase of synaptic strength that is widely believed to be a cellular basis of learning and memory (Bliss and Collingridge 1993). The amygdala possesses the lowest threshold for the induction of kindling (Löscher 1997), an established experimental model of TLE in which daily electrical stimulation results in a gradual progression and intensification of limbic motor seizures (Goddard et al. 1969). Although kindling has been extensively investigated in the context of its clinical relevance to epilepsy and seizure-induced synaptic potentiation, only a few studies that relate to plastic synaptic changes after kindling are available. Therefore, the present study was undertaken to systematically analyze the influence of kindling 48 h after the last seizure on long-term synaptic plasticity, LTP, and long-term depression (LTD) in the lateral nucleus of the amygdala (LA) in rats. The LA was chosen ...

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Calcium currents in pyramidal CA1 neurons in vitro after kindling epileptogenesis in the hippocampus of the rat

Cited by 84 publications

References 49 publications

Chronic Epileptogenic Cellular Alterations in the Limbic System After Status Epilepticus

Chronic Epileptogenic Cellular Alterations in the Limbic System After Status Epilepticus

Chronic Epilepsy in Developing Hippocampal Neurons: Electrophysiologic and Morphologic Features

Kindling-induced changes in plasticity of the rat amygdala and hippocampus

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