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)

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.

scholarly journals Phasic Boosting of Medial Perforant Path-Evoked Granule Cell Output Time-Locked to Spontaneous Dentate EEG Spikes in Awake Rats

1998 ◽  
Vol 79 (6) ◽  
pp. 2825-2832 ◽  
Author(s):  
Clive R. Bramham
Keyword(s):  
Dentate Gyrus ◽  
Slow Wave ◽  
Granule Cell ◽  
Slow Wave Sleep ◽  
Population Spike ◽  
Perforant Path ◽  
Evoked Responses ◽  
Population Spike Amplitude ◽  
Output Time ◽  
Awake Rats

Bramham, Clive R. Phasic boosting of medial perforant path-evoked granule cell output time-locked to spontaneous dentate EEG spikes in awake rats. J. Neurophysiol. 79: 2825–2832, 1998. Dentate spikes (DSs) are positive-going field potential transients that occur intermittently in the hilar region of the dentate gyrus during alert wakefulness and slow-wave sleep. The function of dentate spikes is unknown; they have been suggested to be triggered by perforant path input and are associated with firing of hilar interneurons and inhibition of CA3 pyramidal cells. Here we investigated the effect of DSs on medial perforant path (MPP)-granule cell-evoked transmission in freely moving rats. The MPP was stimulated selectively in the angular bundle while evoked field potentials and the EEG were recorded with a vertical multielectrode array in the dentate gyrus. DSs were identified readily on the basis of their characteristic voltage-versus–depth profile, amplitude, duration, and state dependency. Using on-line detection of the DS peak, the timing of MPP stimulation relative to single DSs was controlled. DS-triggered evoked responses were compared with conventional, manually evoked responses in still-alert wakefulness (awake immobility) and, in some cases, slow-wave sleep. Input-output curves were obtained with stimulation on the positive DS peak (0 delay) and at delays of 50, 100, and 500 ms. Stimulation on the peak DS was associated with a significant increase in the population spike amplitude, a reduction in population spike latency, and a decrease in the field excitatory postsynaptic potential (fEPSP) slope, relative to manual stimulation. Granule cell excitability was enhanced markedly during DSs, as indicated by a mean 93% increase in the population spike amplitude and a leftward shift in the fEPSP-spike relation. Maximum effects occurred at the DS peak, and lasted between 50 and 100 ms. Paired-pulse inhibition of the population spike was unaffected, indicating intact recurrent inhibition during DSs. The results demonstrate enhancement of perforant path-evoked granule cell output time-locked to DSs. DSs therefore may function to intermittently boost excitatory transmission in the entorhinal cortex-dentate gyrus-CA3 circuit. Such a mechanism may be important in the natural induction of long-term potentiation in the dentate gyrus and CA3 regions.

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. III. Comparison of random train and paired impulse stimulation

1988 ◽  
Vol 60 (3) ◽  
pp. 1095-1109 ◽  
Author(s):  
T. W. Berger ◽  
J. L. Eriksson ◽  
D. A. Ciarolla ◽  
R. J. Sclabassi
Keyword(s):  
Nonlinear Systems ◽  
Granule Cell ◽  
Systems Analysis ◽  
Cell Response ◽  
Hippocampal Neurons ◽  
Population Spike ◽  
Perforant Path ◽  
Unanesthetized Animals ◽  
Train Stimulation ◽  
Random Impulse

1. The transformational properties of the network of hippocampal neurons activated monosynaptically and polysynaptically by electrical stimulation of the perforant path were analyzed using random impulse train and paired impulse stimuli. In response to both types of input, the amplitudes of granule cell population spikes evoked in the dentate gyrus were used as the measure of network output. The random stimulus train consisted of a series of 4,064 electrical impulses, with interimpulse intervals determined by a Poisson distribution; the mean interimpulse interval of the train was 500 ms, and the range was 1-5,000 ms. Paired impulse stimuli consisted of pairs of impulses separated by 10-1,200 ms; impulses pairs were delivered once every 20 s. The procedures were applied to both anesthetized and chronically implanted, unanesthetized preparations. 2. Nonlinear systems analysis of population spike responses evoked during random train stimulation revealed that dentate granule cell output to any impulse was highly dependent on the interval since a prior impulse. Data from anesthetized animals showed that population spike amplitudes were markedly suppressed in response to intervals less than 50 ms, facilitated in response to intervals of approximately 100 ms, suppressed slightly in response to intervals of 300-700 ms, and unaffected by intervals greater than 700 ms. Data from unanesthetized animals showed similar results except that facilitation rather than suppression of spike amplitude was observed in response to intervals of 300-700 ms, and could extend to intervals as great as 1,000 ms. 3. The results of paired impulse stimulation applied to the same preparations also showed that granule cell response was highly dependent on interimpulse interval. However, nonlinearities observed with paired impulse stimulation differed from those revealed by a random impulse signal. Compared to results of random train stimulation, a paired impulse format produced greater magnitude spike suppression in response to short interimpulse intervals (e.g., 10-20 ms), maximum facilitation in response to shorter interstimulus intervals (50 ms rather than 100 ms), greater magnitude spike facilitation, and greater suppression in response to intervals greater than or equal to 300 ms. Furthermore, there were virtually no differences in the nonlinearities of granule cell response recorded from anesthetized and unanesthetized animals when a paired impulse format was used, whereas several differences were observed with random train stimuli. 4.(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

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.

Sign in / Sign up

Export Citation Format

Share Document