Effects of postsynaptic GABAB receptor activation on epileptiform activity in hippocampal slices

Xiong, Zhi‐Qi; Stringer, Janet L.

doi:10.1016/s0028-3908(00)00120-9

Cited by 12 publications

(5 citation statements)

References 34 publications

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“…The ipsilesional (left) MVN was isolated and transferred to an interface-type incubation chamber that was continuously perfused with normal aCSF bubbled with 95% O 2 /5% CO 2 (pH 7.4, flow rate 1.8 ml min -1 ) at 3370.21C. Each experiment consisted of a period of recording of MVN neuronal activity in normal aCSF, followed by a switch to modified aCSF containing the following cocktail of neurotransmitter antagonists to achieve partial synaptic blockade: À(À) bicuculline methobromide (20 mM), to block GABA A receptor-mediated transmission [3]; (2S)-( + )-5,5-dimethyl-2-morpholineacetic acid (SCH 50911; 20 mM), to block GABA B receptor-mediated transmission [8]; strychnine hydrochloride (10 mM), to block glycine receptor-mediated transmission [3]; D-(À)-2-amino-5-phosphonopentanoic acid (D-APV; 50 mM) to block Nmethyl-D-asparate receptor-mediated transmission [3]; and 6-cyano-7-nitroquinoxaline-2,3-dione disodium salt (CNQX; 20 mM) to block a-amino-3-hydroxy-5-methylisoxale-4-propionate/kainate receptor-mediated transmission [3].…”

Section: Methodsmentioning

confidence: 99%

Early and late changes in vestibular neuronal excitability after deafferentation

Guilding¹,

Dutia²

2005

NeuroReport

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Medial vestibular nucleus neurons develop a sustained increase in electrophysiological excitability after deafferentation, which may be an important component of 'vestibular compensation' (the behavioural recovery that follows peripheral vestibular lesions). We investigated the effects of gamma-aminobutyric acid, glutamate and glycine receptor blockade on the spontaneous activity of deafferented medial vestibular nucleus neurons in slices, to determine whether changes in synaptic inputs contribute to their increased excitability. Soon after deafferentation (4 h after labyrinthectomy) synaptic blockade had no effect on the elevated in-vitro firing of medial vestibular nucleus neurons, while later (48 h, 1 week), synaptic blockade reduced the elevated activity to normal. Intrinsic mechanisms therefore appear to mediate the elevated excitability of medial vestibular nucleus cells initially after deafferentation. Subsequently, changes in the efficacy of synaptic inputs are implicated, presumably involving intranuclear projections that are preserved in slices.

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Section: Methodsmentioning

confidence: 99%

Early and late changes in vestibular neuronal excitability after deafferentation

Guilding¹,

Dutia²

2005

NeuroReport

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“…Support for a role for neurotransmitters in modulating the rate of ictal burst initiation (frequency) also comes from studies on non-synaptic ictal bursting (where endogenous neurotransmitter release is blocked) in which exogenous application of neuromodulators and neurotransmitters that increase (DL-homocysteic acid, histamine) or decrease (GABA, taurine, adenosine) excitability preferentially modulated burst frequency (Haas and Jefferys, 1984;Lee et al, 1984;Watson and Andrew, 1995;Xiong and Stringer, 2001). Application of either exogenous GABA or baclofen (a GABAB receptor agonist) also promotes the generation of 'pre-ictal' activity and increases population spike amplitude during nonsynaptic bursting (Watson and Andrew, 1995;Xiong and Stringer, 2001) The dependence of ictal burst frequency on neuronal excitability (Fox et al, 2007) could reflect the need for a critical mass of rapidly firing neurons to induce the regenerative potassium build-up correlated with all ictal bursts (Jefferys, 1995). In the 4-AP model, increasing [Ca 2+ ]o and/or [Mg 2+ ]o, which reduces excitability by increasing charge screening, induces a dependence on ionotropic synaptic function (Voskuyl and Albus, 1985;Martin et al, 2001;Barbarosie et al, 2002); this dependence, however, relates in-turn to non-synaptic potassium accumulation (Barbarosie et al, 2002).…”

Section: A Single Theoretical Framework For Ictogenesis In the Hippocmentioning

confidence: 99%

Synaptic transmission modulates while non-synaptic processes govern the transition from pre-ictal to seizure activity in vitro

Bikson

Ruiz‐Nuño

Miranda

et al. 2018

Preprint

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It is well established that non-synaptic mechanisms can generate electrographic seizures after blockade of synaptic function. We investigated the interaction of intact synaptic activity with nonsynaptic mechanisms in the isolated CA1 region of rat hippocampal slices using the "elevated-K + " model of epilepsy. Elevated K + ictal bursts share waveform features with other models of electrographic seizures, including non-synaptic models where chemical synaptic transmission is suppressed, such as the low-Ca 2+ model. These features include a prolonged (several seconds) negative field shift associated with neuronal depolarization and superimposed population spikes. When population spikes are disrupted for up to several seconds, intracellular recording demonstrated that the prolonged suppression of population spikes during ictal activity was due to depolarization block of neurons. Elevated-K + ictal bursts were often preceded by a build-up of "pre-ictal" epileptiform discharges that were characterized as either "slow-transition" (localized and with a gradual increase in population spike amplitude, reminiscent non-synaptic neuronal aggregate formation, presumed mediated by extracellular K + concentrations ([K + ])o accumulation), or "fast-transition" (with a sudden increase in population spike amplitude, presumed mediated by field effects). When ictal activity had a fast-transition it was preceded by fast-transition pre-ictal activity; otherwise population spikes developed gradually at ictal event onset. Addition of bicuculline, a GABAA receptor antagonist, suppressed population spike generation during ictal activity, reduced pre-ictal activity, and increased the frequency of ictal discharges. Nipecotic acid and NNC-711, both of which block GABA reuptake, increased population spike amplitude during ictal bursts and promoted the generation of preictal activity. By contrast, addition of ionotropic glutamate-receptor antagonists (NBQX, D-APV) had no consistent effect on ictal burst waveform or frequency and did not fully suppress pre-ictal activity. Similarly, CGP 55848, a GABAB receptor antagonist, has no significant effect on pre-ictal activity or burst frequency (although it did increase burst duration slightly). Our results are consistent with the hypothesis that non-synaptic mechanisms underpin the generation of ictal bursts in CA1 and that GABAA synaptic mechanisms can shape event development by delaying event initiation and counteracting depolarization block.

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“…Removal of extracellular Ca 2ϩ can produce this effect by preventing synaptic vesicle exocytosis, a process dependent on the influx of Ca 2ϩ into the presynaptic buton. By increasing neuronal excitability by raising extracellular K ϩ levels under nominally Ca 2ϩ free conditions, a number of groups have described a nonsynaptic form of synchronized epileptiform activity Jefferys and Haas 1982;Taylor and Dudek 1982;Thuault et al 2002;Xiong and Stringer 2001). We used similar methods to generate nonsynaptic bursting activity in area CA1 of rat hippocampal slices.…”

Section: R E S U L T Smentioning

confidence: 99%

“…Typically, network synchronization is thought of in terms of classical chemical synaptic communication, although there is a body of evidence to suggest that nonsynaptic, intrinsic electrical activity contributes to network dynamics (Jefferys 1995). Indeed, spontaneous synchronous bursting activity can be observed in hippocampal slices in vitro under conditions whereby Ca 2ϩ -mediated synaptic transmission is abolished Jefferys and Haas 1982;Taylor and Dudek 1982;Thuault et al 2002;Xiong and Stringer 2001). Such activity is induced by increasing [K ϩ ] o and removing, or significantly reducing, [Ca 2ϩ ] o , leading to neuronal depolarization and hyperexcitability through both the shift in the potassium equilibrium potential and reduced divalent ion-mediated surface charge screening.…”

Section: Introductionmentioning

confidence: 99%

“…However, the ionic conductances that underlie this form of synchronous activity remain obscure. The role of several ionic currents have been shown to play a role in generating and/or modulating low Ca 2ϩ bursting activity, including I h (Gill et al 2006), a persistent Na ϩ current (Bikson et al 2003b), and G-protein-coupled K ϩ currents (Xiong and Stringer 2001). In this study we used pharmacological tools that modulate Kv7 channel function to assess the role of I M in hippocampal nonsynaptic synchronous bursting activity.…”

Section: Introductionmentioning

confidence: 99%

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KCNQ/Kv7 Channel Regulation of Hippocampal Gamma-Frequency Firing in the Absence of Synaptic Transmission

Piccinin

Randall²,

Brown³

2006

Journal of Neurophysiology

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Piccinin, S., A. D. Randall, and J. T. Brown. KCNQ/Kv7 channel regulation of hippocampal gamma-frequency firing in the absence of synaptic transmission. J Neurophysiol 95: 3105-3112, 2006. First published February 8, 2006 doi:10.1152/jn.01083.2005. Synchronous neuronal firing can be induced in hippocampal slices in the absence of synaptic transmission by lowering extracellular Ca 2ϩ and raising extracellular K ϩ . However, the ionic mechanisms underlying this nonsynaptic synchronous firing are not well understood. In this study we have investigated the role of KCNQ/Kv7 channels in regulating this form of nonsynaptic bursting activity. Incubation of rat hippocampal slices in reduced (Ͻ0.2 mM) [Ca 2ϩ ] o and increased (6.3 mM) [K ϩ ] o , blocked synaptic transmission, increased neuronal firing, and led to the development of spontaneous periodic nonsynaptic epileptiform activity. This activity was recorded extracellularly as large (4.7 Ϯ 1.9 mV) depolarizing envelopes with superimposed highfrequency synchronous population spikes. These intraburst population spikes initially occurred at a high frequency (about 120 Hz), which decayed throughout the burst stabilizing in the gamma-frequency band (30 -80 Hz). Further increasing [K ϩ ] o resulted in an increase in the interburst frequency without altering the intraburst population spike frequency. Application of retigabine (10 M), a Kv7 channel modulator, completely abolished the bursts, in an XE-991-sensitive manner. Furthermore, application of the Kv7 channel blockers, linopirdine (10 M) or XE-991 (10 M) alone, abolished the gamma frequency, but not the higher-frequency population spike firing observed during low Ca 2ϩ /high K ϩ bursts. These data suggest that Kv7 channels are likely to play a role in the regulation of synchronous population firing activity.

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Effects of postsynaptic GABAB receptor activation on epileptiform activity in hippocampal slices

Cited by 12 publications

References 34 publications

Early and late changes in vestibular neuronal excitability after deafferentation

Early and late changes in vestibular neuronal excitability after deafferentation

Synaptic transmission modulates while non-synaptic processes govern the transition from pre-ictal to seizure activity in vitro

KCNQ/Kv7 Channel Regulation of Hippocampal Gamma-Frequency Firing in the Absence of Synaptic Transmission

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