Distinct Topographical Patterns of Spike-Wave Discharge in Transgenic and Pharmacologically Induced Absence Seizure Models

Lee, Soo-Jung; Hwang, Eunjin; Lee, Mina; Choi, Jee Hyun

doi:10.5607/en.2019.28.4.474

Cited by 8 publications

(11 citation statements)

References 58 publications

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“…The brain functional connectivity is reduced in asymptomatic carriers of LRRK2 mutations and progressively becomes exacerbated at the clinical onset of PD [ 44 , 45 ]. Slowing neuronal oscillation is associated with seizure or epileptiform like events [ 46 , 47 ]. Collectively this indicates the presence of the mutations is sufficient to induce significant functional changes within neurons.…”

Section: Discussionmentioning

confidence: 99%

Neuronal excitatory-to-inhibitory balance is altered in cerebral organoid models of genetic neurological diseases

et al. 2021

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The neuro-physiological properties of individuals with genetic pre-disposition to neurological disorders are largely unknown. Here we aimed to explore these properties using cerebral organoids (COs) derived from fibroblasts of individuals with confirmed genetic mutations including PRNPE200K, trisomy 21 (T21), and LRRK2G2019S, which are associated with Creutzfeldt Jakob disease, Down Syndrome, and Parkinson’s disease. We utilized no known disease/healthy COs (HC) as normal function controls. At 3–4 and 6–10 months post-differentiation, COs with mutations showed no evidence of disease-related pathology. Electrophysiology assessment showed that all COs exhibited mature neuronal firing at 6–10 months old. At this age, we observed significant changes in the electrophysiology of the COs with disease-associated mutations (dCOs) as compared with the HC, including reduced neuronal network communication, slowing neuronal oscillations, and increased coupling of delta and theta phases to the amplitudes of gamma oscillations. Such changes were linked with the detection of hypersynchronous events like spike-and-wave discharges. These dysfunctions were associated with altered production and release of neurotransmitters, compromised activity of excitatory ionotropic receptors including receptors of kainate, AMPA, and NMDA, and changed levels and function of excitatory glutamatergic synapses and inhibitory GABAergic synapses. Neuronal properties that modulate GABAergic inhibition including the activity of Na–K-Cl cotransport 1 (NKCC1) in Cl− homeostasis and the levels of synaptic and extra-synaptic localization of GABA receptors (GABARs) were altered in the T21 COs only. The neurosteroid allopregnanolone, a positive modulator of GABARs, was downregulated in all the dCOs. Treatment with this neurosteroid significantly improved the neuronal communication in the dCOs, possibly through improving the GABAergic inhibition. Overall, without the manifestation of any disease-related pathology, the genetic mutations PRNPE200K, T21, and LRRK2G2019S significantly altered the neuronal network communication in dCOs by disrupting the excitatory-to-inhibitory balance.

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Section: Discussionmentioning

confidence: 99%

Neuronal excitatory-to-inhibitory balance is altered in cerebral organoid models of genetic neurological diseases

et al. 2021

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“…Indeed, absence seizures in GAERS rats are abolished by blocking the firing of these neurons ( Polack et al ., 2009 ), and are more susceptible to ethosuximide applied in the primary somatosensory cortex than the motor cortex or ventrobasal thalamus ( Richards et al , 2003 ; Manning et al , 2004 ). Notably, a recent study ( Lee et al , 2019 ) has shown that whereas spontaneous SWD in PLC-β4 knockout mice originate in the somatosensory cortex, the majority of SWD in the pharmacological γ-hydroxybutyric acid (GHB) model ( Snead, 1992 ; Venzi et al , 2015 ) appear first in the prefrontal cortex, indicating different sites of SWD initiation in different mouse and rat, genetic and pharmacological models as in children with absence seizures (see below).…”

Section: Introductionmentioning

confidence: 99%

“…non-epileptic) animal. Moreover, investigations of absence seizure initiation should carefully consider the different location of the CIN among animal models ( Meeren et al , 2002 ; Studer et al , 2018 ; Lee et al , 2019 ) and between models and children with absence seizures ( Bai et al , 2010 ; Guo et al , 2016 ; Tangwiriyasakul et al , 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures

Crunelli

Lőrincz

McCafferty

et al. 2020

Brain

141

159

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Absence seizures in children and teenagers are generally considered relatively benign because of their non-convulsive nature and the large incidence of remittance in early adulthood. Recent studies, however, show that 30% of children with absence seizures are pharmaco-resistant and 60% are affected by severe neuropsychiatric comorbid conditions, including impairments in attention, cognition, memory and mood. In particular, attention deficits can be detected before the epilepsy diagnosis, may persist even when seizures are pharmacologically controlled and are aggravated by valproic acid monotherapy. New functional MRI-magnetoencephalography and functional MRI-EEG studies provide conclusive evidence that changes in blood oxygenation level-dependent signal amplitude and frequency in children with absence seizures can be detected in specific cortical networks at least 1 min before the start of a seizure, spike-wave discharges are not generalized at seizure onset and abnormal cortical network states remain during interictal periods. From a neurobiological perspective, recent electrical recordings and imaging of large neuronal ensembles with single-cell resolution in non-anaesthetized models show that, in contrast to the predominant opinion, cortical mechanisms, rather than an exclusively thalamic rhythmogenesis, are key in driving seizure ictogenesis and determining spike-wave frequency. Though synchronous ictal firing characterizes cortical and thalamic activity at the population level, individual cortico-thalamic and thalamocortical neurons are sparsely recruited to successive seizures and consecutive paroxysmal cycles within a seizure. New evidence strengthens previous findings on the essential role for basal ganglia networks in absence seizures, in particular the ictal increase in firing of substantia nigra GABAergic neurons. Thus, a key feature of thalamic ictogenesis is the powerful increase in the inhibition of thalamocortical neurons that originates at least from two sources, substantia nigra and thalamic reticular nucleus. This undoubtedly provides a major contribution to the ictal decrease in total firing and the ictal increase of T-type calcium channel-mediated burst firing of thalamocortical neurons, though the latter is not essential for seizure expression. Moreover, in some children and animal models with absence seizures, the ictal increase in thalamic inhibition is enhanced by the loss-of-function of the astrocytic GABA transporter GAT-1 that does not necessarily derive from a mutation in its gene. Together, these novel clinical and experimental findings bring about paradigm-shifting views of our understanding of absence seizures and demand careful choice of initial monotherapy and continuous neuropsychiatric evaluation of affected children. These issues are discussed here to focus future clinical and experimental research and help to identify novel therapeutic targets for treating both absence seizures and their comorbidities.

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“…The spatial distribution of the mouse HD-EEG can be compared to that of the human HD-EEG, providing comparative neuroimaging between the two species. We have proven the use of mouse HD-EEG for retrieving local and global cortical activities, including the somatosensory and motor cortex 19 , prefrontal cortex 1 , anterior versus posterior spindles 20 , and global versus local seizures 21 . Among these studies, we previously provided a full dataset of evoked auditory stimulation under time-locked optogenetic stimulation 22 .…”

Section: Background and Summarymentioning

confidence: 99%

Nine-day continuous recording of EEG and 2-hour of high-density EEG under chronic sleep restriction in mice

Han

Kim

et al. 2022

Sci Data

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This work provides an EEG dataset collected from nine mice during the sleep deprivation (SD) paradigm for the sleep science community. It includes 9-day of continuous recording of the frontal and parietal EEG, accelerometer, and 2-hour of high-density EEG (HD-EEG) under SD and SD-free conditions. Eighteen hours of SD were conducted on 5 consecutive days. The HD-EEG data were saved in the EEGLAB format and stored as the brain imaging data structure (BIDS). These datasets can be used to (i) compare mouse HD-EEG to human HD-EEG, (ii) track oscillatory activities of the sleep EEG (e.g., slow waves, spindles) across the cortical regions under different conditions of sleep pressure, and (iii) investigate the cortical traveling waves in the mouse brain. We also provided Python code for basic analyses of this dataset, including the detection of slow waves and sleep spindles. We hope that our dataset will reveal hidden activities during sleep and lead to a better understanding of the functions and mechanisms of sleep.

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Distinct Topographical Patterns of Spike-Wave Discharge in Transgenic and Pharmacologically Induced Absence Seizure Models

Cited by 8 publications

References 58 publications

Neuronal excitatory-to-inhibitory balance is altered in cerebral organoid models of genetic neurological diseases

Neuronal excitatory-to-inhibitory balance is altered in cerebral organoid models of genetic neurological diseases

Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures

Nine-day continuous recording of EEG and 2-hour of high-density EEG under chronic sleep restriction in mice

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