Explanipedia

Mechanistic insight into the initiation of spreading depolarizations: Is it really all about potassium? Open

Rachel F. Ricks, Connie Mackenzie‐Gray Scott, Andrew J. Trevelyan, R. Ryley Parrish · 2025

Rodent and human seizures demonstrate a dynamic interplay with spreading depolarizations Open

Jacob H Norby, Daniel Hummel, Nathan J. Ricks, John D. Rolston, Shervin Rahimpour , et al. · 2025

On brain stimulation in epilepsy Open

Andrew J. Trevelyan, Victoria S. Marks, R. Graham, Timothy Denison, Andrew Jackson , et al. · 2025

Brain stimulation has, for many decades, been considered as a potential solution for the unmet needs of the many people living with drug-resistant epilepsy. Clinically, there are several different approaches in use, including vagus nerve s…

RNA Sequencing Demonstrates Ex Vivo Neocortical Transcriptomic Changes Induced by Epileptiform Activity in Male and Female Mice Open

Alec Vaughan, Laura J. McMeekin, Kutter Hine, Isaac W Stubbs, Neela K. Codadu , et al. · 2024

Seizures are generally associated with epilepsy but may also be a symptom of many other neurological conditions. A hallmark of a seizure is the intensity of the local neuronal activation, which can drive large-scale gene transcription chan…

AAV8 vector induced gliosis following neuronal transgene expression Open

Faye McLeod, Elaine McDermott, Shermin Mak, Darren Walsh, Mark Turnbull , et al. · 2024

Introduction Expression of light sensitive ion channels by selected neurons has been achieved by viral mediated transduction with gene constructs, but for this to have therapeutic uses, for instance in treating epilepsy, any adverse effect…

Aberrant fast spiking interneuronal activity precedes seizure transitions in humans Open

Edward M. Merricks, Sarita S. Deshpande, Alexander HCW Agopyan-Miu, Elliot H. Smith, Emily Schlafly , et al. · 2024

There is active debate regarding how GABAergic function changes during seizure initiation and propagation, and whether interneuronal activity drives or impedes the pathophysiology. Here, we track cell-type specific firing during spontaneou…

Optogenetic Multiphysical Fields Coupling Model for Implantable Neuroprosthetic Probes Open

Na Dong, Emily L. Johnson, Rolando Berlinguer‐Palmini, Hongze Zhong, Fahimeh Dehkhoda , et al. · 2024

Optogenetic-based neuroprosthetic therapies are increasingly being considered for human trials. However, the optoelectronic design of clinical-grade optogenetic-based neuroprosthetic probes still requires some thought. Design constraints i…

RNA sequencing demonstratesex vivoneocortical transcriptomic changes induced by epileptiform activity in male and female mice Open

Alec Vaughan, Laura J. McMeekin, Kutter Hine, Isaac W Stubbs, Neela K. Codadu , et al. · 2023

Seizures are generally associated with epilepsy but may also be a symptom of many other neurological conditions. A hallmark of a seizure is the intensity of the local neuronal activation, which can drive large-scale gene transcription chan…

Daily rhythm in cortical chloride homeostasis underpins functional changes in visual cortex excitability Open

Enrico Pracucci, R. Graham, Laura Alberio, Gabriele Nardi, Olga Cozzolino , et al. · 2023

Cortical activity patterns are strongly modulated by fast synaptic inhibition mediated through ionotropic, chloride-conducting receptors. Consequently, chloride homeostasis is ideally placed to regulate activity. We therefore investigated …

Cell-type specific and multiscale dynamics of human focal seizures in limbic structures Open

Alexander HCW Agopyan-Miu, Edward M. Merricks, Elliot H. Smith, Guy M. McKhann, Sameer A. Sheth , et al. · 2023

The relationship between clinically accessible epileptic biomarkers and neuronal activity underlying the transition to seizure is complex, potentially leading to imprecise delineation of epileptogenic brain areas. In particular, the patter…

Optogenetic ion pumps differ with respect to the secondary pattern of K + redistribution Open

R. Ryley Parrish, Tom Jackson‐Taylor, Juha Voipio, Andrew J. Trevelyan · 2023

We recently reported that strong activation of the optogenetic chloride pump, halorhodopsin leads to a secondary redistribution of K + ions into the cell, through tonically open, “leak” K + channels. Here we show that this effect is not un…

A debate on the neuronal origin of focal seizures Open

Michael Wenzel, Gilles Huberfeld, David B. Grayden, Marco de Curtis, Andrew J. Trevelyan · 2023

A critical question regarding how focal seizures start is whether we can identify particular cell classes that drive the pathological process. This was the topic for debate at the recent International Conference for Technology and Analysis…

Optogenetic ion pumps differ with respect to the secondary pattern of K+redistribution Open

R. Ryley Parrish, Tom Jackson‐Taylor, Juha Voipio, Andrew J. Trevelyan · 2023

We recently reported that strong activation of the optogenetic chloride pump, Halorhodopsin leads to a secondary redistribution of K + ions into the cell, through tonically open, “leak” K + channels. Here we show that this effect is not un…

Cell-type specific and multiscale dynamics of human focal seizures in limbic structures Open

Alexander HCW Agopyan-Miu, Edward M. Merricks, Elliot H. Smith, Guy M. McKhann, Sameer A. Sheth , et al. · 2023

The relationship between clinically accessible epileptic biomarkers and neuronal activity underlying the seizure transition is complex, potentially leading to imprecise delineation of epileptogenic brain areas. In particular, the pattern o…

Optogenetic stimulation reveals a latent tipping point in cortical networks during ictogenesis Open

R. Graham, R. Ryley Parrish, Laura Alberio, Emily L. Johnson, Laura Owens , et al. · 2022

Brain-state transitions are readily apparent from changes in brain rhythms,1 but are difficult to predict, suggestive that the underlying cause is latent to passive recording methods. Among the most important transitions, clinically, are t…

Indirect Effects of Halorhodopsin Activation: Potassium Redistribution, Nonspecific Inhibition, and Spreading Depolarization Open

R. Ryley Parrish, Connie Mackenzie-Gray Scott, Tom Jackson‐Taylor, Alex Grundmann, Faye McLeod , et al. · 2022

The movement of ions in and out of neurons can exert significant effects on neighboring cells. Here we report several experimentally important consequences of activation of the optogenetic chloride pump, halorhodopsin. We recorded extracel…

Diurnal rhythm in cortical chloride homeostasis underpins functional changes in visual cortex excitability Open

Enrico Pracucci, Robert H. Graham, Laura Alberio, Gabriele Nardi, Olga Cozzolino , et al. · 2022

Fast synaptic inhibition is a primary determinant of cortical activity patterns, and it is mediated predominantly by ionotropic, chloride-conducting receptors. Consequently, modulation of chloride homeostasis is ideally placed to regulate …

Altered synaptic connectivity in an in vitro human model of STXBP1 encephalopathy Open

Faye McLeod, Anna Dimtsi, Amy C Marshall, David Lewis‐Smith, Rhys H. Thomas , et al. · 2022

Early infantile developmental and epileptic encephalopathies are devastating conditions, generally of genetic origin, but the pathological mechanisms often remain obscure. A major obstacle in this field of research is the difficulty of stu…

Closed-loop optogenetic control of the dynamics of neural activity in non-human primates Open

Boubker Zaaimi, Mark Turnbull, Anupam Hazra, Y. Wang, Carolina Gándara , et al. · 2022

Synergistic Positive Feedback Mechanisms Underlying Seizure Initiation Open

Andrew J. Trevelyan, R. Graham, R. Ryley Parrish, Neela K. Codadu · 2022

Investigations into seizure initiation, in recent years, have focused almost entirely upon alterations of interneuronal function, chloride homeostasis, and extracellular potassium levels. In contrast, little attention has been directed tow…

Targeting firing rate neuronal homeostasis can prevent seizures Open

Fred Mulroe, Wei‐Hsiang Lin, Connie Mackenzie‐Gray Scott, Najat Aourz, Yuen Ngan Fan , et al. · 2022

Manipulating firing-rate neuronal homeostasis, which enables neurons to regulate their intrinsic excitability, offers an attractive opportunity to prevent seizures. However, to date, no drug-based interventions have been reported that mani…

Resilient Hippocampal Gamma Rhythmogenesis and Parvalbumin-Expressing Interneuron Function Before and After Plaque Burden in 5xFAD Alzheimer’s Disease Model Open

Connie A. Mackenzie-Gray Scott, Kenneth A. Pelkey, Adam Caccavano, Daniel Abebe, Mandy Lai , et al. · 2022

Recent studies have implicated impaired Parvalbumin Fast-Spiking Interneuron (PVIN) function as a precipitating factor underlying abnormalities in network synchrony, oscillatory rhythms, and cognition associated with Alzheimer’s disease (A…

Targeting neuronal homeostasis to prevent seizures Open

Fred Mulroe, Wei‐Hsiang Lin, Connie Mackenzie-Gray Scott, Najat Aourz, Yuen Ngan Fan , et al. · 2022

Manipulating neuronal homeostasis, which enables neurons to regulate their intrinsic excitability, offers an attractive opportunity to prevent seizures. However, no anticonvulsant compounds have yet been reported that directly manipulate n…

PV-specific loss of the transcriptional coactivator PGC-1α slows down the evolution of epileptic activity in an acute ictogenic model Open

Connie Mackenzie‐Gray Scott, R. Ryley Parrish, Darren Walsh, Claudia Racca, Rita M. Cowell , et al. · 2021

Parvalbumin expressing interneurons are considered to play an important role in regulating cortical activity. We were surprised, therefore, to find that knocking down the transcriptional coactivator, PGC-1α, specifically in this class of i…

Altered synaptic connectivity in anin vitrohuman model of STXBP1 encephalopathy Open

Faye McLeod, Anna Dimtsi, David Lewis‐Smith, Rhys H. Thomas, Gavin J. Clowry , et al. · 2021

Early infantile developmental and epileptic encephalopathies are devastating conditions, generally of genetic origin, but the pathological mechanisms often remain obscure. A major obstacle in this field of research is the difficulty of stu…

A Closed-Loop Optogenetic Platform Open

Dimitrios Firfilionis, Frances Hutchings, Reza Tamadoni, Darren Walsh, Mark Turnbull , et al. · 2021

Neuromodulation is an established treatment for numerous neurological conditions, but to expand the therapeutic scope there is a need to improve the spatial, temporal and cell-type specificity of stimulation. Optogenetics is a promising ar…

PV-specific loss of the transcriptional coactivator PGC-1α slows down the evolution of epileptic activity in an acute ictogenic model Open

R. Ryley Parrish, Connie Mackenzie-Gray-Scott, Darren Walsh, Claudia Racca, Rita M. Cowell , et al. · 2021

The transcriptional coactivator, PGC-1α (peroxisome proliferator activated receptor gamma coactivator 1α), plays a key role coordinating energy requirement within cells. Its importance is reflected in the growing number of psychiatric and …

Diurnal variation in neuronal chloride levels and seizure susceptibility, in neocortex, reflecting changes in activity of chloride-cation-cotransporters Open

Enrico Pracucci, R. Graham, Laura Alberio, Gabriele Nardi, Olga Cozzolino , et al. · 2021

Summary The main inhibitory synaptic currents, gated by gamma-aminobutyric acid (GABA), are mediated by Cl - -conducting channels 1–3 , and are therefore sensitive to changes in the chloride electrochemical gradient. GABAergic activity dic…

Characterization of light penetration through brain tissue, for optogenetic stimulation Open

Emily L. Johnson, Darren Walsh, Frances Hutchings, Rolando Berlinguer‐Palmini, Nikhil Ponon , et al. · 2021

The recent development of optogenetic tools, to manipulate neuronal activity using light, provides opportunities for novel brain-machine interface (BMI) control systems for treating neurological conditions. An issue of critical importance,…

Synergistic positive feedback underlying seizure initiation Open

R. Graham, R. Ryley Parrish, Laura Alberio, Emily L. Johnson, Laura J. Owens , et al. · 2021

Seizure onset is a critically important brain state transition that has proved very difficult to predict accurately from recordings of brain activity. Here we show that an intermittent, optogenetic, stimulation paradigm reveals a latent ch…

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