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

2018 ◽  
Author(s):  
Marom Bikson ◽  
Ana Ruiz-Nuño ◽  
Dolores Miranda ◽  
Greg Kronberg ◽  
Premysl Jiruska ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Receptor Antagonist ◽  
Population Spike ◽  
Depolarization Block ◽  
Spike Amplitude ◽  
Population Spikes ◽  
Population Spike Amplitude ◽  
Ictal Activity ◽  
Electrographic Seizures ◽  
Synaptic Mechanisms

AbstractIt 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 non-synaptic 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-Ca2+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 re-uptake, 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.

Nonlinear systems analysis of the hippocampal perforant path-dentate projection. II. Effects of random impulse train stimulation

1988 ◽  
Vol 60 (3) ◽  
pp. 1077-1094 ◽  
Author(s):  
T. W. Berger ◽  
J. L. Eriksson ◽  
D. A. Ciarolla ◽  
R. J. Sclabassi
Keyword(s):  
Nonlinear Systems ◽  
Granule Cell ◽  
Hippocampal Formation ◽  
Population Spike ◽  
Perforant Path ◽  
Dentate Granule Cell ◽  
Spike Amplitude ◽  
Population Spikes ◽  
Population Spike Amplitude ◽  
Interstimulus Intervals

1. Nonlinear systems analytic techniques were used to characterize transformational properties of the network of neurons activated by perforant path input to the rabbit hippocampus. Trains of 4,064 impulses with randomly varying interimpulse intervals were used to stimulate perforant path fibers, and amplitudes of evoked dentate granule cell population spikes were measured. Interimpulse intervals of the random stimulus train were determined by a Poisson distribution with a mean interimpulse interval of 500 ms, and with intervals ranging from 1 to 5,000 ms. The response of dentate granule cells to this stimulation was assumed to reflect activity in the larger hippocampal network, because other subpopulations of neurons activated monosynaptically and polysynaptically within the hippocampal formation contribute to granule cell excitability through multiple feedforward and feedback pathways. System properties were characterized both for halothane anesthetized and chronically implanted, unanesthetized preparations. 2. Second-order kernel analysis showed that population spike amplitude was highly dependent on interimpulse interval. When population spikes of all latencies were included in the same analysis, stimulation impulses produced near-total suppression of spike amplitude when they were preceded 10-20 ms by another impulse in the train. Spike suppression extended to approximately 50 ms and was inversely related to length of the interimpulse interval. Suppression of granule cell response to intervals within the range of 10-50 ms was not influenced by halothane anesthesia. 3. Interstimulus intervals greater than approximately 50 ms resulted in a facilitation of population spike amplitude, with maximum facilitation occurring in response to intervals of 90-100 ms. The magnitude of maximum facilitation was significantly greater for anesthetized (129%) than for unanesthetized (74%) preparations. The range of intervals resulting in facilitation for unanesthetized animals could extend to 1,000-1,100 ms (average range, 61-714 ms). This was much greater than observed for population spikes recorded from anesthetized animals (50-364 ms), which exhibited suppression in response to intervals of approximately 300-700 ms. 4. Further analysis revealed that the nature of nonlinearities in population spike amplitude may depend on spike latency. For example, population spikes of "short" latency (3-4 or 4-5 ms, depending on the animal) exhibited only facilitation in response to interstimulus intervals of 1-4 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

Serotonin decreases population spike amplitude in hippocampal cells through a pertussis toxin substrate

1987 ◽  
Vol 410 (2) ◽  
pp. 357-361 ◽  
Author(s):  
William P. Clarke ◽  
Michael De Vivo ◽  
Sheryl G. Beck ◽  
Saul Maayani ◽  
Joseph Goldfarb
Keyword(s):  
Pertussis Toxin ◽  
Population Spike ◽  
Spike Amplitude ◽  
Population Spike Amplitude

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

2006 ◽  
Vol 95 (5) ◽  
pp. 3105-3112 ◽  
Author(s):  
S. Piccinin ◽  
A. D. Randall ◽  
J. T. Brown
Keyword(s):  
Synaptic Transmission ◽  
High Frequency ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Neuronal Firing ◽  
Population Spike ◽  
Channel Blockers ◽  
Kv7 Channels ◽  
Population Spikes ◽  
Gamma Frequency

Synchronous neuronal firing can be induced in hippocampal slices in the absence of synaptic transmission by lowering extracellular Ca2+ and raising extracellular K+. 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 (<0.2 mM) [Ca2+]o and increased (6.3 mM) [K+]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 ± 1.9 mV) depolarizing envelopes with superimposed high-frequency 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+]o resulted in an increase in the interburst frequency without altering the intraburst population spike frequency. Application of retigabine (10 μM), a Kv7 channel modulator, completely abolished the bursts, in an XE-991–sensitive manner. Furthermore, application of the Kv7 channel blockers, linopirdine (10 μM) or XE-991 (10 μM) alone, abolished the gamma frequency, but not the higher-frequency population spike firing observed during low Ca2+/high K+ bursts. These data suggest that Kv7 channels are likely to play a role in the regulation of synchronous population firing activity.

Tissue Resistance Changes and the Profile of Synchronized Neuronal Activity During Ictal Events in the Low-Calcium Model of Epilepsy

2004 ◽  
Vol 92 (1) ◽  
pp. 181-188 ◽  
Author(s):  
John E. Fox ◽  
Marom Bikson ◽  
John G. R. Jefferys
Keyword(s):  
High Amplitude ◽  
Spike Frequency ◽  
Population Spike ◽  
Spatial Synchronization ◽  
Population Spikes ◽  
Field Effects ◽  
Tissue Resistance ◽  
Pyramidal Layer ◽  
Population Spike Amplitude ◽  
Main Discharge

Population spikes vary in size during prolonged epileptic (“ictal”) discharges, indicating variations in neuronal synchronization. Here we investigate the role of changes in tissue electrical resistivity in this process. We used the rat hippocampal slice, low-Ca2+ model of epilepsy and measured changes in pyramidal layer extracellular resistance during the course of electrographic seizures. During each burst, population spike frequency decreased, whereas amplitude and spatial synchronization increased; after the main discharge, there could be brief secondary discharges that, in contrast with those in the primary discharge, started with high-amplitude population spikes. Mean resistivity increased from 1,231 Ω.cm immediately before the burst to a maximum of 1,507 Ω.cm during the burst. There was no significant increase during the first 0.5–1 s of the field burst, but resistance then increased (τ ∼ 5 s), reaching its peak at the end of the burst, and then decayed slowly (τ ∼ 10 s). In further experiments, we modulated the efficacy of electrical field effects by changing perfusate osmolarity. Reducing osmolarity by 40–70 mOsm increased preburst resistivity by 19%; it reduced minimum population spike frequency (×0.6–0.7) and increased both maximum population spike amplitude (×1.5–2.3) and spatial synchronization (×1.4–2.5, cross-correlation over 0.5 mm) during bursts. Increasing osmolarity by 20–40 mOsm had the opposite effects. These results suggest that, during each field burst, field effects between neurons gradually become more effective as cells swell, thereby modulating burst dynamics and facilitating the rapid synchronization of secondary discharges.

Evoked Responses of the Dentate Gyrus During Seizures in Developing Gerbils With Inherited Epilepsy

2002 ◽  
Vol 88 (2) ◽  
pp. 783-793 ◽  
Author(s):  
Paul S. Buckmaster ◽  
Emilia H. Wong
Keyword(s):  
Dentate Gyrus ◽  
Granule Cell ◽  
Amplitude Ratio ◽  
Population Spike ◽  
Evoked Responses ◽  
Seizure Onset ◽  
Seizure Severity ◽  
Spike Amplitude ◽  
Population Spike Amplitude ◽  
Fepsp Slope

When they are 1–2 mo old, domesticated Mongolian gerbils begin having initially mild seizures which become more severe with age. To evaluate the development of this increasing seizure severity, we obtained field potential responses of the dentate gyrus to paired-pulse stimulation of the perforant path during seizures. In 18 gerbils that were 1.5–8.0 mo old, 73 seizures were analyzed. We measured population spike amplitude, the slope of the field excitatory postsynaptic potential (fEPSP), and the population spike amplitude ratio (2nd/1st) to evaluate excitatory and inhibitory synaptic processes. In gerbils <2 mo old, exposure to a novel environment was followed by an increase in population spike amplitude and then by seizure onset, but population spike amplitude ratio and fEPSP slope remained at baseline levels, and multiple population spikes were never evoked. As previously reported for chronically epileptic gerbils, these findings provide little evidence of a disinhibitory seizure-initiating mechanism in the dentate gyrus when young gerbils begin having seizures. In young gerbils evoked responses changed little during the behaviorally mild seizures. In contrast, most seizures in older gerbils included generalized convulsions, postictal depression, and evoked responses that changed dramatically. In older gerbils, shortly after seizure onset the dentate gyrus became hyperexcitable. Population spike amplitude and fEPSP slope peaked, and multiple population spikes were evoked, suggesting that mechanisms for seizure amplification and spread are more developed in older gerbils. Next, dentate gyrus excitability decreased precipitously, and population spike amplitude and fEPSP slope diminished. This period of hypoexcitability began before the end of the seizure, suggesting it may contribute to seizure termination. After the convulsive phase of the seizure, older gerbils remained motionless during a period of postictal depression, and population spike amplitude remained suppressed until the abrupt switch to normal exploratory activity. These findings suggest that the mechanisms of postictal depression may suppress granule cell excitability. The population spike amplitude ratio peaked after the convulsive phase and then gradually returned to the baseline level an average of 12 min after seizure onset, suggesting that granule cell inhibition recovers within minutes after a spontaneous seizure. Although it is unclear whether the seizure-related changes in evoked responses are a cause or an effect of increased seizure severity in older gerbils, their analysis provides clues about developmental changes in the mechanisms of seizure spread and termination.

Androsterone sulfate increases dentate gyrus population spike amplitude following tetanic stimulation

2000 ◽  
Vol 71 (5) ◽  
pp. 435-440 ◽  
Author(s):  
Karen Urbanoski ◽  
John Harris ◽  
Karel Gijsbers ◽  
Bernardo Dubrovsky
Keyword(s):  
Dentate Gyrus ◽  
Population Spike ◽  
Tetanic Stimulation ◽  
Spike Amplitude ◽  
Population Spike Amplitude
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