Biology subjects

Lisgaras, C. P.

Publications and source records attributed to Lisgaras, C. P..

3 recordsLinked to original sources

bioRxiv2022

High Frequency Oscillations (250-500Hz) in Animal Models of Alzheimer's Disease

ObjectiveTo test the hypothesis that high frequency oscillations (HFOs) between 250 and 500Hz occur in mouse models of Alzheimers disease (AD) and thus are not unique to epilepsy. MethodsExperiments were conducted in three mouse models of AD: Tg2576 mice that simulate a form of familial AD, presenilin 2 knock-out (PS2KO) mice, and the Ts65Dn model of Downs syndrome. We recorded HFOs using wideband (0.1-500Hz, 2kHz) intra-hippocampal and cortical surface EEG at 1month until 24months-old during wakefulness, slow wave sleep (SWS) and rapid eye movement (REM) sleep. Interictal spikes (IIS) and seizures were also analyzed for the possible presence of HFOs. Comparisons were made to the intra-hippocampal kainic acid and pilocarpine models of epilepsy. ResultsWe describe for the first time that hippocampal and cortical HFOs are a new EEG abnormality in AD mouse models. HFOs occurred in all transgenic mice but no controls. They were also detectable as early as 1month of age and prior to amyloid-{beta} plaque neuropathology. HFOs were most frequent during SWS (vs. REM or wakefulness). Notably, HFOs in the AD and epilepsy models were indistinguishable in both spectral frequency and duration. HFOs also occurred during IIS and seizures in the AD models, although with altered spectral properties compared to isolated HFOs. SignificanceOur data demonstrate that HFOs, an epilepsy biomarker with high translational value, are not unique to epilepsy and thus not disease specific. Our findings also strengthen the idea of hyperexcitability in AD and its significant overlap with epilepsy. HFOs in AD mouse models may serve as an EEG biomarker which is detectable from the scalp and thus amenable to non-invasive detection in people at risk for AD. KEY POINTSO_LIHigh frequency oscillations (HFOs, 250-500Hz) occur in mouse models of Alzheimers disease C_LIO_LIHFOs are detectable from the hippocampus and overlying cortex C_LIO_LIHFOs are most frequent during slow wave sleep C_LIO_LIHFOs in AD mouse models resemble HFOs in two animal models of epilepsy C_LIO_LIHFOs can be detected during interictal spikes and seizures in the AD models C_LI

neuroscience↗

bioRxiv2021

Robust chronic convulsive seizures, high frequency oscillations, and human seizure onset patterns in an intrahippocampal kainic acid model in mice

Intrahippocampal kainic acid (IHKA) has been widely implemented to simulate temporal lobe epilepsy (TLE), but evidence of robust seizures is usually limited. To resolve this problem, we slightly modified previous methods and show robust seizures are common and frequent in both male and female mice. We employed continuous wideband video-EEG monitoring from 4 recording sites to best demonstrate the seizures. We found many more convulsive seizures than most studies have reported. Mortality was low. Analysis of convulsive seizures at 2-4 and 10-12 wks post-IHKA showed a robust frequency (2-4 per day on average) and duration (typically 20-30 sec) at each time. Comparison of the two timepoints showed that seizure burden became more severe in approximately 50% of the animals. We show that almost all convulsive seizures could be characterized as either low-voltage fast or hypersynchronous onset seizures, which has not been reported in a mouse model of epilepsy and is important because these seizure types are found in humans. In addition, we report that high frequency oscillations (>250 Hz) occur, resembling findings from IHKA in rats and TLE patients. Pathology in the hippocampus at the site of IHKA injection was similar to mesial temporal lobe sclerosis and reduced contralaterally. In summary, our methods produce a model of TLE in mice with robust convulsive seizures, and there is variable progression. HFOs are robust also, and seizures have onset patterns and pathology like human TLE. SIGNIFICANCE STATEMENTAlthough the IHKA model has been widely used in mice for epilepsy research, there is variation in outcomes, with many studies showing few robust seizures long-term, especially convulsive seizures. We present an implementation of the IHKA model with frequent convulsive seizures that are robust, meaning they are >10 sec and associated with complex high frequency rhythmic activity recorded from 2 hippocampal and 2 cortical sites. Seizure onset patterns usually matched the low-voltage fast and hypersynchronous seizures in TLE. Importantly, there is low mortality, and both sexes can be used. We believe our results will advance the ability to use the IHKA model of TLE in mice. The results also have important implications for our understanding of HFOs, progression, and other topics of broad interest to the epilepsy research community. Finally, the results have implications for preclinical drug screening because seizure frequency increased in approximately half of the mice after a 6 wk interval, suggesting that the typical 2 wk period for monitoring seizure frequency is insufficient. HIGHLIGHTS* Our implementation of the IHKA model led to robust chronic spontaneous convulsive seizures in mice * Convulsive seizures were synchronized in both hippocampi and two cortical sites * Seizure duration increased between 2-4 wks and 10-12 wks after IHKA * Convulsive seizures fit LVF and HYP types found in human temporal lobe epilepsy * HFOs (>250 Hz) were common, at >1 location, and were both ictal and interictal

neuroscience↗

bioRxiv2021

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.

Convulsive status epilepticus (SE) in immature life is often associated with lasting neurobiological changes. We provoked SE by pentylenetetrazole in postnatal day 20 rat pups and examined communication modalities between the temporal hippocampus and medial entorhinal cortex (mEC) in vitro. After a minimum of 40 days post-SE, we prepared combined temporal hippocampal - medial entorhinal cortex (mEC) slices from conditioned (SE) and naive (N) adult rats and recorded 4-aminopyridine-induced spontaneous epileptiform interictal-like discharges (IED) simultaneously from CA3 and mEC layer V-VI. We analyzed IED frequency and high frequency oscillations (HFOs) in intact slices and after surgical separation of hippocampus from mEC, by two successive incisions (Schaffer collateral cut, Parasubiculum cut). In all slices, IED frequency was higher in CA3 vs mEC and Raster plots indicated no temporal coincidence between them either in intact or in CA1-cut slices. IED frequency was significantly higher in SE mEC, but similar in SE and N CA3, independently of connectivity state. Ripples (R) and Fast Ripples (FR) coincided with IEDs and their power differed between SE and N intact slices, both in CA3 and mEC. CA3 FR/R ratios were higher in the absence of mEC. Moreover, SE (vs N) slices showed significantly higher FR/R ratios independently of the presence of mEC. Taken together, these findings suggest lasting effects of immature SE in network dynamics governing hippocampal-entorhinal communication which may impact adult cognitive, behavioral and/or seizure threshold sequalae. HIGHLIGHTSO_LIEarly-life Status Epilepticus (SE) impacts on the adult hippocampal - entorhinal communication in the in vitro 4-AP model C_LIO_LIPost-SE CA3 output decreases in HFO power with no change in interictal discharge frequency C_LIO_LIPost-SE mEC output increases both in HFO power and interictal discharge frequency C_LIO_LIInterictal HFO dynamics in CA3-mEC change upon the connectivity state of the two areas and priorhistory of early-life SE C_LI

neuroscience↗