Biology subjects

Egert, U.

Publications and source records attributed to Egert, U..

5 recordsLinked to original sources

bioRxiv2024

PEACOC - Detecting and classifying a wide range of epileptiform activity patterns in rodents

Epileptiform activity (EA) manifests in diverse patterns of hypersynchronous network activity. Fundamental research mostly addresses two extreme patterns, individual epileptiform spikes and seizures. We developed PEACOC to detect and classify a wide range of EA patterns in local field potentials. PEACOC delimits EA patterns as bursts of epileptiform spikes, and classifies these bursts according to spike load. In EA from kainate-injected mice, burst patterns displayed a continuum of spike loads. With PEACOC, we partitioned this continuum into bursts of high, medium and low spike load. High-load bursts resembled electrographic seizures. The EA patterns automatically retrieved by PEACOC were reproducible and comparable across animals and laboratories. PEACOC has been employed to diagnose the overall burden of EA in individual mice, and to describe epileptic dynamics at multiple time-scales. We here further report that the rate of high-load bursts was anti-correlated to granule cell dispersion in the dentate gyrus.

neuroscience↗

bioRxiv2023

On-demand low-frequency stimulation for seizure control: efficacy and behavioral implications

Mesial temporal lobe epilepsy (MTLE), the most common form of focal epilepsy in adults, is often refractory to medication and associated with hippocampal sclerosis. Deep brain stimulation represents an alternative treatment option for drug-resistant patients who are ineligible for resective brain surgery. In clinical practice, closed-loop stimulation at high frequencies is applied to interrupt ongoing seizures, yet with a high incidence of false detections, the drawback of delayed seizure-suppressive intervention and limited success in sclerotic tissue. More recently, hippocampal low-frequency stimulation (LFS) has been shown to reduce excitability in clinical settings and prevent seizures in experimental MTLE when applied continuously. However, as the hippocampus is important for navigation and memory, it would be beneficial to stimulate it only on-demand to reduce its exposure to LFS pulses, and to investigate LFS-related effects on cognition. Using the intrahippocampal kainate mouse model, which recapitulates the key features of MTLE, we developed an on-demand LFS setup and investigated its effects on spontaneous seizure activity and hippocampal function. Specifically, our online detection algorithm monitored epileptiform activity in hippocampal local field potential recordings and identified short epileptiform bursts preceding focal seizure clusters, triggering hippocampal LFS to stabilize the network state. In addition, we investigated the acute influence of LFS on behavioral performance, including anxiety-like behavior in the light-dark box test, spatial and non-spatial memory in the object location memory and novel object recognition test, as well as spatial navigation and long-term memory in the Barnes maze. Compared to open-loop stimulation protocols, on-demand LFS was more efficient in preventing focal seizure clusters, as the strong anti-epileptic effect was achieved with a reduced stimulation load. In behavioral tests, chronically epileptic mice were as mobile as healthy controls but showed increased anxiety, an altered spatial learning strategy and impaired memory performance. Most importantly, our experiments ruled out deleterious effects of hippocampal LFS on cognition and even showed alleviation of deficits in long-term memory recall. Taken together, our findings may provide a promising alternative to current therapies, overcoming some of their major limitations, and inspire further investigation of LFS for seizure control in MTLE.

neuroscience↗

bioRxiv2021

Intracortical probe arrays with silicon backbone and microelectrodes on thin polyimide wings enable long-term stable recordings in vivo

ObjectiveRecording and stimulating neuronal activity across different brain regions requires interfacing at multiple sites using dedicated tools while tissue reactions at the recording sites often prevent their successful long-term application. This implies the technological challenge of developing complex probe geometries while keeping the overall footprint minimal, and of selecting materials compatible with neural tissue. While the potential of soft materials in reducing tissue response is uncontested, the implantation of these materials is often limited to reliably target neuronal structures across large brain volumes. ApproachWe report on the development of a new multi-electrode array exploiting the advantages of soft and stiff materials by combining 7-m-thin polyimide wings carrying platinum electrodes with a silicon backbone enabling a safe probe implantation. The probe fabrication applies microsystems technologies in combination with a temporal wafer fixation method for rear side processing, i.e., grinding and deep reactive ion etching, of slender probe shanks and electrode wings. The wing-type neural probes are chronically implanted into the entorhinal-hippocampal formation in the mouse for in vivo recordings of freely behaving animals. Main resultsProbes comprising the novel wing-type electrodes have been realized and characterized in view of their electrical performance and insertion capability. Chronic electrophysiological in vivo recordings of the entorhinal-hippocampal network in the mouse of up to 104 days demonstrated a stable yield of channels containing identifiable multi-unit and single-unit activity outperforming probes with electrodes residing on a Si backbone. SignificanceThe innovative fabrication process using a process compatible, temporary wafer bonding allowed to realize new Michigan style probe arrays. The wing-type probe design enables a precise probe insertion into brain tissue and long-term stable recordings of unit activity due to the application of a stable backbone and 7-m-thin probe wings provoking locally a minimal tissue response and protruding from the glial scare of the backbone.

neuroscience↗

bioRxiv2020

Optogenetic low-frequency stimulation of dentate granule cells prevents seizure generation in experimental epilepsy

Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy in adults and is typically associated with hippocampal sclerosis and drug-resistant seizures. As an alternative to curative epilepsy surgery, brain stimulation evolves as a promising approach for seizure-interference. However, particularly in MTLE with severe hippocampal sclerosis, current stimulation protocols are often not effective. Here, we show that optogenetic low-frequency stimulation (oLFS) of entorhinal afferents exhibits unprecedented anti-ictogenic effects in chronically epileptic mice. Photostimulation at 1 Hz resulted in an almost complete suppression of focal seizures, independent of the degree of hippocampal sclerosis. Furthermore, by performing oLFS for 30 min before a pro-convulsive stimulus, seizure generalization was successfully prevented. Finally, acute slice experiments revealed a decreased excitability upon oLFS, which may partially explain the observed anti-epileptic effects. Taken together, our results suggest that oLFS of entorhinal afferents constitutes a promising approach for seizure control in MTLE.

physiology↗

bioRxiv2018

Dynamics of multiple interacting excitatory and inhibitory populations with delays

A network consisting of excitatory and inhibitory (EI) neurons is a canonical model for understanding cortical network activity. In this study, we extend the EI network model and investigate how its dynamical landscape can be enriched when it interacts with another excitatory (E) population with transmission delays. Through analysis and simulations of a rate model and a spiking network model, we study the transition from stationary to oscillatory states by analyzing the Hopf bifurcation structure in terms of two network parameters: 1) transmission delay between the EI subnetwork and the E population and 2) inhibitory couplings that induce oscillatory activity in the EI subnetwork. We find that the critical coupling strength can strongly modulate as a function of transmission delay, and consequently the stationary state is interwoven intricately with oscillatory states generating different frequency modes. This leads to the emergence of an isolated stationary state surrounded by multiple oscillatory states and cross-frequency coupling develops at the bifurcation points. We identify the possible network motifs that induce oscillations and examine how multiple oscillatory states come together to enrich the dynamical landscape.

neuroscience↗