New devices that use targeted electrical stimulation to treat refractory localization-related epilepsy have shown great promise, although it is not well known which targets most effectively prevent the initiation and spread of seizures. To better understand how the brain transitions from healthy to seizing on a local scale, we induced focal epileptiform activity in the visual cortex of five anesthetized cats with local application of the GABA blocker picrotoxin while simultaneously recording local field potentials on a high-resolution electrocorticography array and laminar depth probes. Epileptiform activity appeared in the form of isolated events, revealing a consistent temporal pattern of ictogenesis across animals with interictal events consistently preceding the appearance of seizures. Based on the number of spikes per event, there was a natural separation between seizures and shorter interictal events. Two distinct spatial regions were seen: an epileptic focus that grew in size as activity progressed, and an inhibitory surround that exhibited a distinct relationship with the focus both on the surface and in the depth of the cortex. Epileptiform activity in the cortical laminae was seen concomitant with activity on the surface. Focus spikes appeared earlier on electrodes deeper in the cortex, suggesting that deep cortical layers may be integral to recruiting healthy tissue into the epileptic network and could be a promising target for interventional devices. Our study may inform more effective therapies to prevent seizure generation and spread in localization-related epilepsies. NEW & NOTEWORTHY We induced local epileptiform activity and recorded continuous, high-resolution local field potentials from the surface and depth of the visual cortex in anesthetized cats. Our results reveal a consistent pattern of ictogenesis, characterize the spatial spread of the epileptic focus and its relationship with the inhibitory surround, and show that focus activity within events appears earliest in deeper cortical layers. These findings have potential implications for the monitoring and treatment of refractory epilepsy.
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http://dx.doi.org/10.1152/jn.00764.2017 | DOI Listing |
Alzheimers Dement
December 2024
Department of Bioengineering, University of California, Los Angeles, CA, USA, Los Angeles, CA, USA.
Background: The initiation of amyloid plaque deposition signifies a crucial stage in Alzheimer's disease (AD) progression, which often coincides with the disruption of neural circuits and cognitive decline. While the role of excitatory-inhibitory balance is increasingly recognized in AD pathophysiology, targeted therapies to modulate this balance remain underexplored. This study investigates the effect of perampanel, a selective non-competitive AMPA receptor antagonist, in modulating neurophysiological changes in hAPP-J20 transgenic Alzheimer's mice.
View Article and Find Full Text PDFBackground: Seizures in Alzheimer's Disease (AD) are increasingly recognized to occur and can increase cognitive decline and reduce survival compared to unaffected age-matched peers (Lyou et al. 2018). Administration of antiseizure medicines (ASMs) to AD patients with epileptiform activity may improve cognition (Vossel et al.
View Article and Find Full Text PDFBackground: Early-onset Alzheimer's disease (EOAD) associated with amyloid precursor protein (APP) duplications or presenilin (PSEN) variants increases risk of seizures. Targeting epileptiform activity with antiseizure medicine (ASM) administration to AD patients may beneficially attenuate cognitive decline (Vossel et al, JAMA Neurology 2021). However, whether mechanistically distinct ASMs differentially suppress seizures in discrete EOAD models is understudied (Lehmann et al, Neurochem Res 2021).
View Article and Find Full Text PDFGenes (Basel)
December 2024
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
Background: (absent, small, or homeotic-like 1), a histone methyltransferase, has been identified as a high-risk gene for autism spectrum disorder (ASD). We previously showed that postnatal severe deficiency in the prefrontal cortex (PFC) of male and female mice caused seizures. However, the synaptic mechanisms underlying autism-like social deficits and seizures need to be elucidated.
View Article and Find Full Text PDFIt is well known that activation of NMDA receptors can trigger long-term synaptic depression (LTD) and that a morphological correlate of this functional plasticity is spine retraction and elimination. Recent studies have led to the surprising conclusion that NMDA-induced spine shrinkage proceeds independently of ion flux and requires the initiation of protein synthesis, highlighting an unappreciated contribution of mRNA translation to non-ionotropic NMDAR signaling. Here we used NMDA-induced spine shrinkage in slices of mouse hippocampus as a readout to investigate this novel modality of synaptic transmission.
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