Epileptiform response of CA1 neurones to convulsant stimulation by cyclothiazide, kainic acid and pentylenetetrazol in anaesthetized rats

Qian, Binbin; Sun, Yajie; Wu, Zijian; Wan, Li; Chen, Lulan; Kong, Sue; Zhang, Bin-Hong; Zhang, Fayong; Wang, Zhenyu; Wang, Yun

doi:10.1016/j.seizure.2010.12.016

Cited by 17 publications

(14 citation statements)

References 43 publications

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“…Using this model, our results demonstrated that extrasynaptic GABA A Rs were downregulated by ~50% Recently, several studies have shown that CTZ is a potent convulsant capable of inducing epileptiform activity both in vivo and in cultured hippocampal neurons [16,17,25] , as well as evoking seizure behavior in freely-moving animals [26] . In the current study, we further extended this epilepsy model to hippocampal slices.…”

Section: Discussionmentioning

confidence: 64%

Activation of extrasynaptic GABAA receptors inhibits cyclothiazide-induced epileptiform activity in hippocampal CA1 neurons

Wan

Liu

et al. 2014

Neurosci. Bull.

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Extrasynaptic GABA(A) receptors (GABA(A)Rs)-mediated tonic inhibition is reported to involve in the pathogenesis of epilepsy. In this study, we used cyclothiazide (CTZ)-induced in vitro brain slice seizure model to explore the effect of selective activation of extrasynaptic GABA(A)Rs by 4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridine-3-ol (THIP) on the CTZ-induced epileptiform activity in hippocampal neurons. Perfusion with CTZ dose-dependently induced multiple epileptiform peaks of evoked population spikes (PSs) in CA1 pyramidal neurons, and treatment with THIP (5 μmol/L) significantly reduced the multiple PS peaks induced by CTZ stimulation. Western blot showed that the δ-subunit of the GABA(A)R, an extrasynaptic specific GABA(A)R subunit, was also significantly down-regulated in the cell membrane 2 h after CTZ treatment. Our results suggest that the CTZ-induced epileptiform activity in hippocampal CA1 neurons is suppressed by the activation of extrasynaptic GABA(A)Rs, and further support the hypothesis that tonic inhibition mediated by extrasynaptic GABA(A)Rs plays a prominent role in seizure generation.

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Section: Discussionmentioning

confidence: 64%

Activation of extrasynaptic GABAA receptors inhibits cyclothiazide-induced epileptiform activity in hippocampal CA1 neurons

Wan

Liu

et al. 2014

Neurosci. Bull.

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“…The hippocampal CA1 region is one of the brain areas in which PTZ induces highly synchronized epileptiform burst activity31. We therefore hypothesized that a reduced PTZ seizure threshold would be reflected in an increased excitability of CA1 pyramidal neurons.…”

Section: Resultsmentioning

confidence: 99%

Cognitive deficits caused by a disease-mutation in the α3 Na+/K+-ATPase isoform

Holm

Isaksen

Glerup

et al. 2016

Sci Rep

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The Na+/K+-ATPases maintain Na+ and K+ electrochemical gradients across the plasma membrane, a prerequisite for electrical excitability and secondary transport in neurons. Autosomal dominant mutations in the human ATP1A3 gene encoding the neuron-specific Na+/K+-ATPase α3 isoform cause different neurological diseases, including rapid-onset dystonia-parkinsonism (RDP) and alternating hemiplegia of childhood (AHC) with overlapping symptoms, including hemiplegia, dystonia, ataxia, hyperactivity, epileptic seizures, and cognitive deficits. Position D801 in the α3 isoform is a mutational hotspot, with the D801N, D801E and D801V mutations causing AHC and the D801Y mutation causing RDP or mild AHC. Despite intensive research, mechanisms underlying these disorders remain largely unknown. To study the genotype-to-phenotype relationship, a heterozygous knock-in mouse harboring the D801Y mutation (α3+/D801Y) was generated. The α3+/D801Y mice displayed hyperactivity, increased sensitivity to chemically induced epileptic seizures and cognitive deficits. Interestingly, no change in the excitability of CA1 pyramidal neurons in the α3+/D801Y mice was observed. The cognitive deficits were rescued by administration of the benzodiazepine, clonazepam, a GABA positive allosteric modulator. Our findings reveal the functional significance of the Na+/K+-ATPase α3 isoform in the control of spatial learning and memory and suggest a link to GABA transmission.

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“…The acute models mentioned elsewhere in this review use slices of hippocampus and other forebrain structures maintained in vitro or in vivo (Prince, 1972;Qian et al, 2011;Stafstrom et al, 2009;Tabashidze and Mares, 2011). Many of them rely on blocking GABA A receptor mediated inhibition with drugs such as picrotoxin, bicuculline or penicillin (Dingledine and Gjerstad, 1979;Schwartzkroin and Prince, 1978).…”

Section: Acute Models Of Epilepsy-convulsant Drugsand Changes In Extrmentioning

confidence: 99%

Mechanisms of physiological and epileptic HFO generation

Jefferys

Prida

Wendling

et al. 2012

Progress in Neurobiology

269

238

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High frequency oscillations (HFO) have a variety of characteristics: band-limited or broad-band, transient burst-like phenomenon or steady-state. HFOs may be encountered under physiological or under pathological conditions (pHFO). Here we review the underlying mechanisms of oscillations, at the level of cells and networks, investigated in a variety of experimental in vitro and in vivo models. Diverse mechanisms are described, from intrinsic membrane oscillations to network processes involving different types of synaptic interactions, gap junctions and ephaptic coupling. HFOs with similar frequency ranges can differ considerably in their physiological mechanisms. The fact that in most cases the combination of intrinsic neuronal membrane oscillations and synaptic circuits are necessary to sustain network oscillations is emphasized. Evidence for pathological HFOs, particularly fast ripples, in experimental models of epilepsy and in human epileptic patients is scrutinized. The underlying mechanisms of fast ripples are examined both in the light of animal observations, in vivo and in vitro, and in epileptic patients, with emphasis on single cell dynamics. Experimental observations and computational modeling have led to hypotheses for these mechanisms, several of which are considered here, namely the role of out-ofphase firing in neuronal clusters, the importance of strong excitatory AMPA-synaptic currents and recurrent inhibitory connectivity in combination with the fast time scales of IPSPs, ephaptic coupling and the contribution of interneuronal coupling through gap junctions. The statistical behaviour of fast ripple events can provide useful information on the underlying mechanism and can help to further improve classification of the diverse forms of HFOs.

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Epileptiform response of CA1 neurones to convulsant stimulation by cyclothiazide, kainic acid and pentylenetetrazol in anaesthetized rats

Cited by 17 publications

References 43 publications

Activation of extrasynaptic GABAA receptors inhibits cyclothiazide-induced epileptiform activity in hippocampal CA1 neurons

Activation of extrasynaptic GABAA receptors inhibits cyclothiazide-induced epileptiform activity in hippocampal CA1 neurons

Cognitive deficits caused by a disease-mutation in the α3 Na+/K+-ATPase isoform

Mechanisms of physiological and epileptic HFO generation

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