A5042239715- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Epilepsy research and treatment
- Photoreceptor and optogenetics research
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neural Engineering
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- EEG and Brain-Computer Interfaces
- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Memory and Neural Mechanisms
- Histone Deacetylase Inhibitors Research
- Functional Brain Connectivity Studies
- Identity, Memory, and Therapy
- Adipose Tissue and Metabolism
- Lysosomal Storage Disorders Research
- Pancreatic function and diabetes
- MicroRNA in disease regulation
- Mitochondrial Function and Pathology
- Signaling Pathways in Disease
- Neurological and metabolic disorders
- RNA regulation and disease
- Lipid Membrane Structure and Behavior
Brigham Young University
2022-2025
Xenon Pharmaceuticals (Canada)
2022-2024
Newcastle University
2018-2023
University of Newcastle Australia
2021
The Neurosciences Foundation
2018-2019
University of Alabama at Birmingham
2010-2016
Benzodiazepine-resistant status epilepticus is an ongoing clinical challenge. Burman et al. show that longer seizure duration a useful indicator of benzodiazepine resistance, and resistance caused by changes in GABAA receptor-mediated synaptic transmission. The findings could help optimise current management protocols.
ABSTRACT Aged animals show functional alterations in hippocampal neurons that lead to deficits synaptic plasticity and changes cognitive function. Transcription of immediate‐early genes (IEGs), including Egr 1, is necessary for processes such as long‐term potentiation memory consolidation. Here, we an age‐related reduction the transcription 1 dentate gyrus following spatial behavior, whereas area CA1, reduced at rest, but its can be effectively driven by behavior levels equivalent those...
There is a rapid interneuronal response to focal activity in cortex, which restrains laterally propagating activity, including spreading epileptiform activity. The involves intense activation of both parvalbumin- and somatostatin-expressing interneurons. Interneuronal bursting time-locked glutamatergic barrages the pre-ictal period. Ca2+ imaging using conditional expression GCaMP6f provides an accurate readout evolving firing patterns types interneuron. profiles two classes are temporally...
Voltage-gated sodium channel (NaV) inhibitors are used to treat neurological disorders of hyperexcitability such as epilepsy. These drugs act by attenuating neuronal action potential firing reduce excitability in the brain. However, all currently available NaV-targeting antiseizure medications nonselectively inhibit brain channels NaV1.1, NaV1.2, and NaV1.6, which potentially limits efficacy therapeutic safety margins these drugs. Here, we report on XPC-7724 XPC-5462, represent a new class...
Recent advances in chromatin biology have identified a role for epigenetic mechanisms the regulation of neuronal gene expression changes, necessary process proper synaptic plasticity and memory formation. Experimental evidence dynamic remodeling influencing transcription postmitotic neurons grew from initial reports describing posttranslational modifications histones, including phosphorylation acetylation occurring various brain regions during consolidation. An accumulation recent studies,...
DNA methylation is an epigenetic modification that essential for the development and mature function of central nervous system. Due to relevance this transcriptional control gene expression, it often necessary examine changes in patterns with both single-nucleotide resolution. Here, we describe in-depth basic protocol direct bisulfite sequencing isolated from brain tissue, which will permit assessment status at individual genes as well cytosine molecules/nucleotides within a genomic region....
Seizure termination has been linked to spreading depolarizations (SDs) in experimental epilepsy models, and SDs have recently suggested protect against seizures. The precise mechanism, however, remains unclear. Additionally, the co-occurrence of with human seizures debated. In this study, we found that are a prominent feature following ictal events both clinical recordings (n=20 from 7 patients) using direct-current amplifiers 0 Mg2+ model ictogenesis rodent brain slices (n=17)....
Temporal lobe epilepsy (TLE) patients exhibit signs of memory impairments even when seizures are pharmacologically controlled. Surprisingly, the underlying molecular mechanisms involved in TLE-associated remain elusive. Memory consolidation requires epigenetic transcriptional regulation genes hippocampus; therefore, we aimed to determine how DNA methylation affect learning-induced transcription memory-permissive epileptic hippocampus.Using kainate rodent model TLE and focusing on...
Much debate exists about how the brain transitions into an epileptic seizure. One source of confusion is that there are likely to be critical differences between experimental seizure models. To address this, we have compared evolving activity patterns in two widely used vitro models discharges. Brain slices from young adult mice were prepared same way and bathed either 0 Mg2+ or 100 µmol/L 4AP artificial cerebrospinal fluid. We found while local field potential recordings epileptiform...
Brain-state transitions are readily apparent from changes in brain rhythms,1 but difficult to predict, suggestive that the underlying cause is latent passive recording methods. Among most important transitions, clinically, starts of seizures. We here show an 'active probing' approach may have several benefits for epileptic management, including by helping predict these transitions. used mice expressing optogenetic actuator, channelrhodopsin, pyramidal cells, allowing this population be...
Local neocortical and hippocampal territories show different sterotypical patterns of acutely evolving, epileptiform activity. Neocortical entorhinal networks tonic-clonic-like events, but the main do not, unless it is relayed from other areas. Transitions in pattern locally recorded activity can be indicative a shift source pathological activity, may spread through both synaptic non-synaptic means. Hippocampal promoted by 4-aminopyridine inhibited GABAB receptor agonists, appears far more...
Abstract Parvalbumin-expressing interneurons in cortical networks are coupled by gap junctions, forming a syncytium that supports propagating epileptiform discharges, induced 4-aminopyridine. It remains unclear, however, whether these events occur under more natural states, without pharmacological blockade. In particular, we investigated propagation also happens when extracellular K + rises, as is known to following intense network activity, such during seizures. We examined how increasing...
Temporal lobe epilepsy (TLE) is a type of focal characterized by spontaneous recurrent seizures originating from the hippocampus. The epigenetic reprogramming hypothesis epileptogenesis suggests that development TLE associated with alterations in gene transcription changes resulting hyperexcitable network TLE. DNA 5-methylcytosine (5-mC) an mechanism has been chronic epilepsy. However, contribution 5-hydroxymethylcytosine (5-hmC), product 5-mC demethylation Ten-Eleven Translocation (TET)...
The movement of ions in and out neurons can exert significant effects on neighboring cells. Here we report several experimentally important consequences activation the optogenetic chloride pump, halorhodopsin. We recorded extracellular K + concentration ([K ] extra ) neocortical brain slices prepared from young adult mice (both sexes) which express halorhodopsin pyramidal Strong induced a pronounced drop [K that persisted for duration illumination. Pharmacological blockade channels reduced...
Abstract Seizure onset is a critically important brain state transition that has proved very difficult to predict accurately from recordings of activity. Here we show an intermittent, optogenetic, stimulation paradigm reveals latent change in dendritic excitability tightly correlated the seizure Our data how precipitous nature can be understood terms multiple, synergistic positive feedback mechanisms: raised intracellular Cl - and extracellular K + , coupled reduced threshold for plateau...
Changes in gene expression are an important mechanism by which activity levels regulated the nervous system. It is not known, however, how network influences interneurons; since they themselves provide negative feedback form of synaptic inhibition, there exists a potential conflict between their cellular homeostatic tendencies and those network. We present means examining this issue, utilizing simple vitro models showing different patterns intense activity. found that degree concurrent...
Seizures are generally associated with epilepsy but may also be a symptom of many other neurological conditions. A hallmark seizure is the intensity local neuronal activation, which can drive large-scale gene transcription changes. Such changes in transcriptional profile likely alter function, thereby contributing to pathological process. Therefore, there strong clinical imperative characterize how expression changed by activity. To this end, we developed simplified ex vivo technique for...
High-density multi-electrode array (HD-MEA) has enabled neuronal measurements at high spatial resolution to record local field potentials (LFP), extracellular action potentials, and network-wide recording on an extended scale. While we have advanced systems with over 4,000 electrodes capable of data 20 kHz, it still presents computational challenges handle, process, extract, view information from these large recordings. We created a method, open-source toolkit built in Python, rendered web...