Region-specific Effects of Early-life Status Epilepticus on the Adult Hippocampal CA3 – Medial Entorhinal Cortex Circuitry In vitro: Focus on Interictal Spikes and Concurrent High-frequency Oscillations

Lisgaras, Christos Panagiotis; Mikroulis, Apostolos; Psarropoulou, Caterina

doi:10.1016/j.neuroscience.2021.04.030

Cited by 5 publications

(8 citation statements)

References 88 publications

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“…The longer IED duration in Mg 2+ ‐free ACSF was also reflected in the longer duration of both Rs and FRs. However, the higher 1st PS amplitude of IEDs was only reflected on the higher R amplitude in the Mg 2+ ‐free model, in line to earlier findings, where IED changes were associated to only one band (R or FR) changes 3,4 …”

Section: Discussionsupporting

confidence: 89%

“…However, the 1st PS amplitude of IEDs was only reflected on the higher R amplitude in the Mg 2+free model, in line to earlier findings, where IED changes were associated to only one band (R or FR) changes. 3,4 In both models, Rs and FRs were detected earlier than the onset of IEDs reflecting the synchronization mechanisms at play before the onset of synchronous discharges and indicating that HFOs are a precipitating factor bringing about the epileptiform discharges. A similar finding of Rs preceding spikes has been reported in an EEG study.…”

Section: Hfo Differences In the Two Modelsmentioning

confidence: 93%

“…Filtering electrophysiological recordings obtained in vitro has revealed High Frequency Oscillations (HFOs) coinciding with IEDs, [1][2][3][4] that is, Ripples (Rs, 80-200 Hz) and Fast Ripples (FRs, 200-600 Hz), which are frequency bands obtained also in EEG recordings. HFOs are an integral part of normal brain function, 5 including memory, [5][6][7] however, specific HFO types have been linked to specific seizure types or discharges.…”

Section: Introductionmentioning

confidence: 99%

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Timing differences between HFOs and interictal epileptiform discharges generated in vitro by different mechanisms in rat hippocampal slices: A novel approach

2022

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Objective: To investigate the effect of generating mechanism on the relationship between interictal-like epileptiform discharges (IEDs) and the underlying High Frequency Oscillations (HFOs; Ripples, R, and Fast Ripples, FR).Methods: Synchronous spontaneous IEDs were recorded from the CA1 area of hippocampal slices from adult rats, perfused by Mg 2+ -free ACSF (n = 41slices/14 animals) or 4-aminopyridine (50 μM, n = 37slices/16 animals); IED filtering revealed Rs and FRs and several metrics were calculated and compared (amplitude, duration, relative onset, time lag, % overlap, peak frequency, peak power, FR/R).Results: Longer IEDs and higher 1st Population Spike (PS) amplitude in Mg 2+free ACSF (vs 4-AP; P < .001, P < .001) correlated with longer duration and higher amplitude Rs (P < .0001, P = .001) and longer duration FRs (P < .001). In both media, Rs and FRs appeared before IED onset with Rs preceding FRs; R-and FR-IED lag (P = .008, P = .01) as well as R-FR lag (P = .04) were significantly longer in Mg 2+ -free ACSF vs in 4-AP. R peak frequency and power were higher in Mg 2+free ACSF, while no such differences were observed in FRs. Inter-model differences were mostly reflected in Rs, not FRs, suggesting that mechanisms unique to R generation are more active in Mg 2+ -free ACSF vs in 4-AP. FRs appeared to contribute equally to IEDs irrespective of generating mechanism.Significance: Several of the metrics used, particularly those regarding the timing between HFOs and IEDs, appear to correlate with the synchronizing mechanism and we propose that they may be useful when investigating antiepileptic substance effects on neuronal network activity.

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Section: Discussionsupporting

confidence: 89%

Section: Hfo Differences In the Two Modelsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Timing differences between HFOs and interictal epileptiform discharges generated in vitro by different mechanisms in rat hippocampal slices: A novel approach

2022

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“…Molecular mechanisms of complex pathophysiological phenomena are often studied in their chemical models. For instance, pentylenetetrazol is widely employed to model epilepsy (1), while mitochondrial impairment in neurodegenerative diseases is often modeled by exposure of animals to inhibitors of the respiratory chain (2,3). The high sensitivity of mitochondrial complex II to inhibition by malonate and 3-nitropropionic acid (3-NP) is used to model Huntington's disease (2,4).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of 2-Oxoglutarate Dehydrogenase as a Chemical Model of Acute Hypobaric Hypoxia

2021

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Both hypoxia and inhibition of 2-oxoglutarate dehydrogenase complex (OGDHC) are known to change cellular amino acid pools, but the quantitative comparison of the metabolic and physiological outcomes has not been done. We hypothesize that OGDHC inhibition models metabolic changes caused by hypoxia, as both perturb the respiratory chain function, limiting either the NADH (OGDHC inhibition) or oxygen (hypoxia) supply. In the current study, we quantify the changes in the amino acid metabolism after OGDHC inhibition in the highly sensitive to hypoxia cerebellum and compare them to the earlier characterized changes after acute hypobaric hypoxia. In addition, the associated physiological effects are characterized and compared. A specific OGDHC inhibitor succinyl phosphonate (SP) is shown to act similar to hypoxia, increasing levels of many amino acids in the cerebellum of non-pregnant rats, without affecting those in the pregnant rats. Compared with hypoxia, stronger effects of SP in non-pregnant rats are observed on the levels of cerebellar amino acids, electrocardiography (ECG), and freezing time. In pregnant rats, hypoxia affects ECG and behavior more than SP, although none of the stressors significantly change the levels of cerebellar amino acids. The biochemical differences underlying the different physiological actions of SP and hypoxia are revealed by correlation analysis of the studied parameters. The negative correlations of cerebellar amino acids with OGDHC and/or tryptophan, shown to arise after the action of SP and hypoxia, discriminate the overall metabolic action of the stressors. More negative correlations are induced in the non-pregnant rats by hypoxia, and in the pregnant rats by SP. Thus, our findings indicate that the OGDHC inhibition mimics the action of acute hypobaric hypoxia on the cerebellar amino acid levels, but a better prediction of the physiological outcomes requires assessment of integral network changes, such as increases in the negative correlations among the amino acids, OGDHC, and/or tryptophan.

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“…HFOs in epilepsy are known to be associated with IIS both in vitro , 33 in vivo 34 and in recordings from epilepsy patients. 35 Thus, we asked if AD HFOs were also associated with IIS because IIS are common in patients with AD.…”

Section: Resultsmentioning

confidence: 99%

High Frequency Oscillations (250-500Hz) in Animal Models of Alzheimer’s Disease and Two Animal Models of Epilepsy

Lisgaras

Scharfman

2022

Preprint

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Objective: To test the hypothesis that high frequency oscillations (HFOs) between 250 and 500Hz occur in mouse models of Alzheimer's disease (AD). Methods: Experiments were conducted in three mouse models of AD: Tg2576 mice (n=9) that overexpress the Swedish mutation of amyloid precursor protein, presenilin 2 knock-out (PS2KO) mice (n=8), and the Ts65Dn model of Down's syndrome (n=9). We recorded HFOs using wideband (0.1-500Hz, 2kHz) intra-hippocampal and cortical surface EEG at 1month until 24months of age during wakefulness, slow wave sleep (SWS) and rapid eye movement (REM) sleep. EEG was also recorded using the intra-hippocampal kainic acid and pilocarpine models of epilepsy to compare HFOs in AD and epilepsy models. Interictal spikes (IIS) and seizures in the AD models were also analyzed for the possible presence of HFOs. Results: We describe for the first time hippocampal and cortical HFOs as a new EEG abnormality in AD mouse models. HFOs occurred in all transgenic mice and but no controls (p<0.05). HFOs were most frequent during SWS (vs. REM or wakefulness, p<0.05). HFOs in the AD and epilepsy models were indistinguishable in both spectral frequency and duration (p>0.05). HFOs also occurred during IIS and seizures in the AD models, although with altered spectral properties compared to isolated HFOs (p<0.05). Interpretation: Our data demonstrate a new EEG biomarker in AD mouse models which is detectable from the scalp and thus amenable to non-invasive detection in people at risk for AD.

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Region-specific Effects of Early-life Status Epilepticus on the Adult Hippocampal CA3 – Medial Entorhinal Cortex Circuitry In vitro: Focus on Interictal Spikes and Concurrent High-frequency Oscillations

Cited by 5 publications

References 88 publications

Timing differences between HFOs and interictal epileptiform discharges generated in vitro by different mechanisms in rat hippocampal slices: A novel approach

Timing differences between HFOs and interictal epileptiform discharges generated in vitro by different mechanisms in rat hippocampal slices: A novel approach

Inhibition of 2-Oxoglutarate Dehydrogenase as a Chemical Model of Acute Hypobaric Hypoxia

High Frequency Oscillations (250-500Hz) in Animal Models of Alzheimer’s Disease and Two Animal Models of Epilepsy

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