A5035552445- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- Mast cells and histamine
- Neuroscience of respiration and sleep
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Ion channel regulation and function
- Nerve injury and regeneration
- Olfactory and Sensory Function Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Nicotinic Acetylcholine Receptors Study
- Sulfur Compounds in Biology
- Biochemical Acid Research Studies
- S100 Proteins and Annexins
- Neurological disorders and treatments
- Memory and Neural Mechanisms
- Mitochondrial Function and Pathology
- Biochemical Analysis and Sensing Techniques
- Sleep and Wakefulness Research
- Amino Acid Enzymes and Metabolism
Université Laval
2022-2023
University of Toronto
2010-2020
Queen's University
2012-2013
Significance Huntington’s disease (HD) is a fatal neurodegenerative disorder that currently has no cure. Although HD classically considered motor disorder, patients experience learning and memory deficits years before the onset of symptoms, these resemble those observed in mouse models. In this work, using transgenic models HD, we demonstrate action neurotransmitter GABA switched from inhibitory to excitatory. By treating mice with clinically used diuretic (bumetanide), which restores GABA,...
KCC2 is a neuron-specific K+-Cl– cotransporter essential for establishing the Cl- gradient required hyperpolarizing inhibition in central nervous system (CNS). highly localized to excitatory synapses where it regulates spine morphogenesis and AMPA receptor confinement. Aberrant function contributes human neurological disorders including epilepsy neuropathic pain. Using functional proteomics, we identified KCC2-interactome mouse brain determine KCC2-protein interactions that regulate...
Abstract Olfactory processing is thought to be actively modulated by the top-down input from cortical regions, but behavioural function of these signals remains unclear. Here we find that feedback anterior olfactory nucleus pars medialis (mAON) bidirectionally modulates sensitivity and olfaction-dependent behaviours. To identify a limbic tunes this mAON switch, further demonstrate optogenetic stimulation ventral hippocampal inputs sufficient alter
Abstract Amyotrophic lateral sclerosis is a fatal disease resulting from motor neuron degeneration in the cortex and spinal cord. Cortical hyperexcitability hallmark feature of amyotrophic accompanied by decreased intracortical inhibition. Using electrophysiological patch-clamp recordings, we revealed parvalbumin interneurons to be hypoactive late pre-symptomatic SOD1*G93A mouse model sclerosis. We discovered that using adeno-associated virus-mediated delivery chemogenetic technology...
Synaptic inhibition depends on a transmembrane gradient of chloride, which is set by the neuron-specific K+-Cl− co-transporter KCC2. Reduced KCC2 levels in neuronal membrane contribute to generation epilepsy, neuropathic pain, and autism spectrum disorders; thus, it important characterize mechanisms regulating expression. In present study, we determined role KCC2-protein interactions total surface Using quantitative immunofluorescence cultured mouse hippocampal neurons, discovered that...
Hydrogen sulfide (H2S) is a novel neurotransmitter that has been shown to influence cardiovascular functions as well and corticotrophin hormone (CRH) secretion. Since the paraventricular nucleus of hypothalamus (PVN) central relay center for autonomic endocrine functions, we sought investigate effects H2S on neuronal population PVN. Whole cell current clamp recordings were acquired from PVN neurons sodium hydrosulfide hydrate (NaHS) was bath applied at various concentrations (0.1, 1, 10, 50...
Abstract Hyperexcitability in cells throughout the corticospinal tract is a presymptomatic feature of amyotrophic lateral sclerosis (ALS) associated with lethal motor degeneration 1–6 . Disinhibition possible cause this hyperexcitability, potentially implicating central nervous system-specific potassium-chloride cotransporter, KCC2, core regulator strength GABAergic neurotransmission linked to several neurological disorders 7–11 Here, we show that KCC2 downregulated membrane cortex neurons...
Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated with the loss of cortical and spinal motor neurons (MNs) muscle degeneration (Kiernan et al. in Lancet 377:942–955, 2011). In preclinical setting, functional tests that can detect early changes function rodent models ALS are critical to understanding etiology disease treatment development. Here, we established string-pulling paradigm forelimb hindlimb deficits SOD1 mouse model earlier than traditional...
Several hydrogen sulfide (H2S) donors have been produced for commercial use, all of which assumed to similar if not identical effects in their ability deliver H2S. The identification H2S‐catalyzing enzymes the paraventricular nucleus hypothalamus (PVN) led us examine sodium (NaHS) on excitability PVN neurons. Bath application 50 and 10mM caused 75% responsive neurons hyperpolarize (n=28, −13.58±1.51mV), while at 1 0.1mM depolarized (n=8, 9.627±2.82mV ). lack availability this donor continue...
Hydrogen sulphide (H2S) has been observed as having a protective role against gastro‐intestinal inflammation. H2S‐catalyzing enzymes are expressed in the paraventricular nucleus of hypothalamus (PVN). Previous findings suggest that, if stimulated, PVN can produce inflammatory responses GI tract. To understand effects H2S PVN, we examined donor, sodium hydrogen (NaHS) on excitability neurons. Whole‐cell current clamp recordings from rat neurons slice preparations were performed. Bath...
Abstract KCC2 is a neuron-specific K + -Cl − cotransporter essential for establishing the Cl gradient required hyperpolarizing inhibition. highly localized to excitatory synapses where it regulates spine morphogenesis and AMPA receptor confinement. Aberrant function contributes numerous human neurological disorders including epilepsy neuropathic pain. Using unbiased functional proteomics, we identified KCC2-interactome in mouse brain determine KCC2-protein interactions that regulate...