Retrosplenial Cortex Contributes to Network Changes during Seizures in the GAERS Absence Epilepsy Rat Model

Wachsmuth, Lydia; Datunashvili, Maia; Kemper, Katharina; Albers, Franziska; Lambers, Henriette; Lüttjohann, Annika; Kreitz, Silke; Budde, Thomas; Faber, Cornelius

doi:10.1093/texcom/tgab023

Cited by 12 publications

(11 citation statements)

References 76 publications

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“…Demyelinated axons may not be able to meet these requirements, thereby resulting in decreased SWD generation during early remyelination. In addition, changes in network organization during seizures like the segregation of cortical regions from the remaining brain may play a role ( Wachsmuth et al. 2021 ).…”

Section: Discussionmentioning

confidence: 99%

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Modulation of pacemaker channel function in a model of thalamocortical hyperexcitability by demyelination and cytokines

et al. 2022

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A consensus is yet to be reached regarding the exact prevalence of epileptic seizures or epilepsy in multiple sclerosis (MS). In addition, the underlying pathophysiological basis of the reciprocal interaction among neuroinflammation, demyelination, and epilepsy remains unclear. Therefore, a better understanding of cellular and network mechanisms linking these pathologies is needed. Cuprizone-induced general demyelination in rodents is a valuable model for studying MS pathologies. Here, we studied the relationship among epileptic activity, loss of myelin, and pro-inflammatory cytokines by inducing acute, generalized demyelination in a genetic mouse model of human absence epilepsy, C3H/HeJ mice. Both cellular and network mechanisms were studied using in vivo and in vitro electrophysiological techniques. We found that acute, generalized demyelination in C3H/HeJ mice resulted in a lower number of spike–wave discharges, increased cortical theta oscillations, and reduction of slow rhythmic intrathalamic burst activity. In addition, generalized demyelination resulted in a significant reduction in the amplitude of the hyperpolarization-activated inward current (Ih) in thalamic relay cells, which was accompanied by lower surface expression of hyperpolarization-activated, cyclic nucleotide-gated channels, and the phosphorylated form of TRIP8b (pS237-TRIP8b). We suggest that demyelination-related changes in thalamic Ih may be one of the factors defining the prevalence of seizures in MS.

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Section: Discussionmentioning

confidence: 99%

“…2019 ). Future studies have to identify possible alteration in the epileptic cortical initiation zone or segregation of the cortex from subcortical areas in the course of seizures following demyelination ( Wachsmuth et al. 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Modulation of pacemaker channel function in a model of thalamocortical hyperexcitability by demyelination and cytokines

et al. 2022

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“…The RSC has long been studied for its role in generating seizure activity due to its anatomical connections and, therefore, as a target to modulate seizure activity. 9 fMRI data from a mouse model of genetic epilepsy have shown the RSC forming more connections as a hub between subcortical and cortical regions in the epileptic rats. 9 Apparent difference in the hub dynamics in the RSC across different epilepsy models indicates model specific mechanisms in epileptogenesis.…”

Section: Commentarymentioning

confidence: 99%

“… 9 fMRI data from a mouse model of genetic epilepsy have shown the RSC forming more connections as a hub between subcortical and cortical regions in the epileptic rats. 9 Apparent difference in the hub dynamics in the RSC across different epilepsy models indicates model specific mechanisms in epileptogenesis. Additional analyses on different centralities could have provided insights into identifying important nodes based on different features.…”

Section: Commentarymentioning

confidence: 99%

Targeting Epileptogenesis: A Conceptual Black Hole or Light at the End of the Tunnel?

Hwang¹,

Kadam²

2021

Epilepsy Curr

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Objective: The current study aims to investigate functional brain network representations during the early period of epileptogenesis. Methods: Eighteen rats with the intrahippocampal kainate model of mesial temporal lobe epilepsy were used for this experiment. Functional magnetic resonance imaging (fMRI) measurements were made 1 week after status epilepticus, followed by 2-4-month electrophysiological and video monitoring. Animals were identified as having (1) developed epilepsy (E+, n = 9) or (2) not developed epilepsy (EÀ, n = 6). Nine additional animals served as controls. Graph theory analysis was performed on the fMRI data to quantify the functional brain networks in all animals prior to the development of epilepsy. Spectrum clustering with the network features was performed to estimate their predictability in epileptogenesis. Results: Our data indicated that E+ animals showed an overall increase in functional connectivity strength compared to EÀ and control animals. Global network features and small-worldness of EÀrats were similar to controls, whereas E+ rats demonstrated increased small-worldness, including increased reorganization degree, clustering coefficient, and global efficiency, with reduced shortest path length. A notable classification of the combined brain network parameters was found in E+ and EÀanimals. For the local network parameters, the EÀrats showed increased hubs in sensorimotor cortex, and decreased hubness in hippocampus. The E+ rats showed a complete loss of hippocampal hubs, and the appearance of new hubs in the prefrontal cortex. We also observed that lesion severity was not related to epileptogenesis. Significance: Our data provide a view of the reorganization of topographical functional brain networks in the early period of epileptogenesis and how it can significantly predict the development of epilepsy. The differences from EÀanimals offer a potential means for applying noninvasive neuroimaging tools for the early prediction of epilepsy.

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“…Especially in small animal fMRI, physiological noise must be studied carefully, since measurements are often acquired under anesthesia, which alter physiological processes (Gao et al, 2017;Paasonen et al, 2018;van Alst et al, 2019) compared to the awake condition. Small animal fMRI is valuable for translational research, since it offers numerous options such as studying specific disease models (Tenney et al, 2003;Tristao Pereira et al, 2021;Wachsmuth et al, 2021), pharmacological (Haensel et al, 2015) and surgical interventions (Chen et al, 2019) as well as combining MRI with electrophysiological (Pan et al, 2010;Kosten et al, 2022) and optical recordings (Schulz et al, 2012;Albers et al, 2018;Lake et al, 2020;Ioanas et al, 2022). To avoid incorrect translational conclusions, it is crucial to investigate physiological noise and to develop correction methods for commonly performed preclinical experiments.…”

Section: Introductionmentioning

confidence: 99%

The impact of vasomotion on analysis of rodent fMRI data

et al. 2023

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IntroductionSmall animal fMRI is an essential part of translational research in the cognitive neurosciences. Due to small dimensions and animal physiology preclinical fMRI is prone to artifacts that may lead to misinterpretation of the data. To reach unbiased translational conclusions, it is, therefore, crucial to identify potential sources of experimental noise and to develop correction methods for contributions that cannot be avoided such as physiological noise. Aim of this study was to assess origin and prevalence of hemodynamic oscillations (HDO) in preclinical fMRI in rat, as well as their impact on data analysis.MethodsFollowing the development of algorithms for HDO detection and suppression, HDO prevalence in fMRI measurements was investigated for different anesthetic regimens, comprising isoflurane and medetomidine, and for both gradient echo and spin echo fMRI sequences. In addition to assessing the effect of vasodilation on HDO, it was studied if HDO have a direct neuronal correlate using local field potential (LFP) recordings. Finally, the impact of HDO on analysis of fMRI data was assessed, studying both the impact on calculation of activation maps as well as the impact on brain network analysis. Overall, 303 fMRI measurements and 32 LFP recordings were performed in 71 rats.ResultsIn total, 62% of the fMRI measurements showed HDO with a frequency of (0.20 ± 0.02) Hz. This frequent occurrence indicated that HDO cannot be generally neglected in fMRI experiments. Using the developed algorithms, HDO were detected with a specificity of 95%, and removed efficiently from the signal time courses. HDO occurred brain-wide under vasoconstrictive conditions in both small and large blood vessels. Vasodilation immediately interrupted HDO, which, however, returned within 1 h under vasoconstrictive conditions. No direct neuronal correlate of HDO was observed in LFP recordings. HDO significantly impacted analysis of fMRI data, leading to altered cluster sizes and F-values for activated voxels, as well as altered brain networks, when comparing data with and without HDO.DiscussionWe therefore conclude that HDO are caused by vasomotion under certain anesthetic conditions and should be corrected during fMRI data analysis to avoid bias.

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Retrosplenial Cortex Contributes to Network Changes during Seizures in the GAERS Absence Epilepsy Rat Model

Cited by 12 publications

References 76 publications

Modulation of pacemaker channel function in a model of thalamocortical hyperexcitability by demyelination and cytokines

Modulation of pacemaker channel function in a model of thalamocortical hyperexcitability by demyelination and cytokines

Targeting Epileptogenesis: A Conceptual Black Hole or Light at the End of the Tunnel?

The impact of vasomotion on analysis of rodent fMRI data

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