A5051447285- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Zebrafish Biomedical Research Applications
- Memory and Neural Mechanisms
- Neural dynamics and brain function
- Epilepsy research and treatment
- EEG and Brain-Computer Interfaces
- Neurogenesis and neuroplasticity mechanisms
- Mitochondrial Function and Pathology
- Piezoelectric Actuators and Control
- Diet and metabolism studies
- Electrowetting and Microfluidic Technologies
- Epigenetics and DNA Methylation
- Neonatal and fetal brain pathology
- Image Processing Techniques and Applications
- Genetics and Neurodevelopmental Disorders
- Ion channel regulation and function
- Platelet Disorders and Treatments
- Axon Guidance and Neuronal Signaling
- Immunodeficiency and Autoimmune Disorders
- Microtubule and mitosis dynamics
- Nuclear Structure and Function
- Microfluidic and Bio-sensing Technologies
- Receptor Mechanisms and Signaling
- Cannabis and Cannabinoid Research
Alberta Children's Hospital
2016-2025
University of Calgary
2016-2025
Allen Institute for Brain Science
2024
Center for Neurosciences
2024
University of California, San Diego
2020-2023
Rady Children's Hospital-San Diego
2020-2023
Grigore T. Popa University of Medicine and Pharmacy
2022
Queen Mary University of London
2017
William Harvey Research Institute
2017
Canada's Michael Smith Genome Sciences Centre
2017
Despite the development of newer anti-seizure medications over past 50 years, 30-40% patients with epilepsy remain refractory to treatment. One explanation for this lack progress is that current screening process largely biased towards transmembrane channels and receptors, ignores intracellular proteins enzymes might serve as efficacious molecular targets. Here, we report a novel drug platform harnesses power zebrafish genetics combines it in vivo bioenergetics assays uncover therapeutic...
SLC13A5 encodes a citrate transporter highly expressed in the brain and is important for regulating intra- extracellular levels. Mutations this gene cause rare infantile epilepsy characterized by lifelong seizures, developmental delays, behavioral deficits, poor motor progression, language impairments. individuals respond poorly to treatment options; yet drug discovery programs are limited due paucity of animal models that phenocopy human symptoms. Here, we used CRISPR/Cas9 create...
Background: The mechanisms underlying the clinical effects of CBD remain poorly understood. Given increasing evidence for CBD's on mitochondria, we sought to examine in more detail whether impacts mitochondrial function and neuronal integrity. Methods: We utilized BE(2)-M17 neuroblastoma cells or acutely isolated brain mitochondria from rodents using a Seahorse extracellular flux analyzer fluorescent spectrofluorophotometer assay. Mitochondrial ion channel activity hippocampal long-term...
Abstract The piriform cortex makes strong interconnections with limbic structures (amygdala, entorhinal and hippocampus) that are involved in memory processing. These connections have also been implicated the development of temporal lobe epilepsy. However, little is known about how neurones this region may change during seizure genesis. Here we tested hypothesis kindling model epilepsy GABA A receptor‐mediated inhibition altered cortex. To do performed whole‐cell patch‐clamp recordings brain...
We have previously shown that after kindling (a model of temporal lobe epilepsy), the neuroactive steroid tetrahydrodeoxycorticosterone (THDOC) was unable to augment GABA type A receptor (GABA(A))-mediated synaptic currents occurring on pyramidal cells piriform cortex. Phosphorylation GABA(A) receptors has been alter activity THDOC, so we tested hypothesis induces changes in phosphorylation and this accounts for loss efficacy. To assay whether are more phosphorylated kindling, examined state...
Abstract Previous studies have suggested that the patterns of innervation and high interconnectivity piriform cortex (PC) provide for strong olfactory hippocampal memory; however, these same attributes may create seizurogenic tendencies. Thus, understanding this wiring is important from a physiological pathophysiological perspective. Distinct interneurons expressing differing calcium binding proteins (CBPs), parvalbumin (PV), calbindin (CB), calretinin (CR), been shown to exist in PC....
How the integrity of laminar structures in postnatal brain is maintained impacts neuronal functions. Ndel1, mammalian homolog NuDE from filamentous fungus Aspergillus nidulans, an atypical microtubule (MT)-associated protein that was initially investigated contexts neurogenesis and migration. Constitutive knock-out mice for Ndel1 are embryonic lethal, thereby necessitating creation a conditional to probe roles brains. Here we report CA1 pyramidal neurons postnatally lacking (Ndel1 knock-out)...
Abstract Neural recordings made to date through various approaches—both in-vitro or in-vivo—lack high spatial resolution and a signal-to-noise ratio (SNR) required for detailed understanding of brain function, synaptic plasticity, dysfunction. These shortcomings in turn deter the ability further design diagnostic, therapeutic strategies fabrication neuro-modulatory devices with feedback loop systems. We report here on simulation fully configurable neural micro-electrodes that can be used...
Purpose: Resolution of inflammation is an active homeostatic process controlled by proresolving lipids and peptides.We characterized this during epileptogenesis to test whether boosting resolution mechanisms prevents or mediates disease modifications.Method: Our analyses were done in the hippocampus mice exposed status epilepticus (SE) their sham controls, patients who died ≤5 ≥7 days from SE autopsy controls.Mice studied 2 h, 24 h 72 after (epileptogenesis) evoked intraamygdala injection...
In optic neuropathies, including glaucoma, retinal ganglion cells (RGCs) die. Cell transplantation and endogenous regeneration offer strategies for repair, however, developmental programs required this to succeed are incompletely understood. To address this, we explored cellular reprogramming with transcription factor (TF) regulators of RGC development which were integrated into human pluripotent stem (PSCs) as inducible gene cassettes. When the pioneer NEUROG2 was combined RGC-expressed TFs...
Abstract Dysfunction of nuclear distribution element-like 1 (Ndel1) is associated with schizophrenia, a neuropsychiatric disorder characterized by cognitive impairment and seizures as comorbidity. The levels Ndel1 are also altered in human models epilepsy, chronic condition whose hallmark feature the occurrence spontaneous recurrent typically comorbid conditions including learning memory deficits, anxiety, depression. In this study, we analyzed behaviors mice postnatally deficient for...
In the perirhinal cortex of seizure prone (SP) rats, GABA(A)-mediated miniature inhibitory postsynaptic currents (mIPSCs) are smaller in amplitude but have longer deactivation phases than mIPSCs recorded normal control (NC; outbred) rats. These differences correlated to relatively higher alpha1 subunit expression NC rat strains and alpha2, alpha3, alpha5 SP strain. Using patch-clamp recording, we investigated how neurosteroids tetrahydrodeoxcorticosterone (THDOC) allopregnanolone at...
Abstract The glycoprotein Reelin maintains neuronal positioning and regulates plasticity in the adult brain. deficiency has been associated with neurological diseases. We recently showed that is depleted mice a targeted disruption of Ndel1 gene forebrain postnatal excitatory neurons (Ndel1 conditional knockout (CKO)). CKO exhibit fragmented microtubules CA1 pyramidal neurons, profound deterioration hippocampus shortened lifespan (~10 weeks). Here we report (of both sexes) experience spatial...
Abstract We tested the hypothesis that experimentally produced epilepsy (by kindling) may induce changes in GABA A receptor expression some but not all interneuron populations. Using laser capture microdissection and quantitative polymerase chain reaction (QPCR) analysis, α subunit calbindin‐ (CB ir ) parvalbumin‐ (Parv immunoreactive interneurons was compared between normal brains which amygdala kindled seizure responses were permanently established. Two weeks after last response, Cb...
Here, we explore the mechanism of action isoxylitone (ISOX), a molecule discovered in plant Delphinium denudatum, which has been shown to have anticonvulsant properties. Patch-clamp electrophysiology assayed activity ISOX on voltage-gated sodium channels (VGSCs) both cultured neurons and brain slices isolated from controls rats with experimental epilepsy(kindling model). Quantitative transcription polymerase chain reaction (qRT-PCR) (QPCR) assessed brain-derived neurotrophic factor (BDNF)...
Abstract Objective KCNA1 mutations are associated with a rare neurological movement disorder known as episodic ataxia type 1 (EA1), and epilepsy is common comorbidity. Current medications provide only partial relief for and/or seizures, making new drugs needed. Here, we characterized zebrafish kcna1a −/− model of EA1 compared the efficacy first‐line therapy carbamazepine in to Kcna1 rodents. Methods CRISPR/Cas9 mutagenesis was used introduce mutation sixth transmembrane segment protein....
Mutations in cytoskeletal proteins can cause early infantile and childhood epilepsies by misplacing newly born neurons altering neuronal connectivity. In the adult epileptic brain, disruption is often viewed as being secondary to aberrant activity and/or death, hence simply represents an epiphenomenon. Here, we review emerging evidence collected animal models human studies implicating cytoskeleton a potential causative factor epileptogenesis. Based on evidence, propose that may be important...
There are applications where different objective lenses have to be used for microscope imaging. Rotary nose-pieces cannot when larger objectives required and there is a physical space limitation. It also very difficult time consuming change the lens manually locate focus on same spot again; This may prevent any attempt automating an image-guided robot-assisted procedure using images with lenses. A linear changing mechanism has been developed which makes it possible slide under microscope....
Patch clamping is an electrophysiological technique that permits the measurement of ion channel activity in many different kinds cells. Placement patch clamp electrodes using micromanipulators a time consuming and complicated task due to lack depth perception microscope optics constrained physical environment. In order simplify this process, software platform has been created user easily perform not only single electrode recordings but multiple ones. The provides capabilities for automatic...
Patch clamping is used in electrophysiology to study single or multiple ion channels cells. Multiple micropipettes are as electrodes collect data from several Placement of these a time consuming and complicated task due the lack depth perception, limited view through microscope lens possibility collisions between micro-pipettes. To aid this process, computer-assisted approach developed using image processing techniques applied images obtained microscope. Image algorithms perform...
SLC13A5 encodes a citrate transporter highly expressed in the brain important for regulating intra- and extracellular levels. Mutations this gene cause rare infantile epilepsy characterized by lifelong seizures, developmental delays, behavioral deficits, poor motor progression, language impairments. individuals respond poorly to treatment options; yet drug discovery programs are limited due paucity of animal models that phenocopy human symptoms. Here, we used CRISPR/Cas9 create...
The electroencephalogram (EEG) is crucial for real-time brain physiology research in epilepsy. However, maternal care reliance limits its use immature rodents. Our "pup-in-cup" setup overcomes this, enabling continuous, uninterrupted video-EEG/electromyogram (EMG) recordings neonatal rats. This protocol details the steps video-EEG/EMG system setup, EEG headmount implantation, and recording continuous traces from postnatal days 4-12. For complete on execution of this protocol, please refer to...