A5046548037- Ion channel regulation and function
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurobiology and Insect Physiology Research
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Mitochondrial Function and Pathology
- Alzheimer's disease research and treatments
- Neurological Disease Mechanisms and Treatments
- Pancreatic function and diabetes
- Ion Channels and Receptors
- RNA regulation and disease
- Connexins and lens biology
University of British Columbia
2016-2023
Queen's University
2013-2016
Astrocytes display complex morphologies with an array of fine extensions extending from the soma and primary thick processes. Until use genetically encoded calcium indicators (GECIs) selectively expressed in astrocytes, Ca2+ signaling was only examined processes astrocytes where Ca2+-sensitive fluorescent dyes could be imaged. GECI imaging revealed a previously unsuspected pattern spontaneous transients that has not been observed without chronic expression GECIs, raising potential concerns...
Neuronal activation is fundamental to information processing by the brain and requires mitochondrial energy metabolism. Mitochondrial Ca2+ uptake uniporter (MCU) has long been implicated in control of metabolism intracellular signalling, but its importance neuronal function remains unclear. Here, we used situ electrophysiology two-photon imaging Ca2+, cytosolic NAD(P)H test relevance MCU pyramidal neuron signalling during action potential firing. We demonstrate that tuned enhanced firing...
Intracellular chloride ion concentration ([Cl-]i) homeostasis is critical for excitatory/inhibitory balance and volume regulation in neurons. We quantitatively map spatiotemporal dendritic [Cl-]i dynamics during N-methyl-d-aspartate (NMDA) excitotoxicity to determine how Cl- changes contribute localized swelling (blebbing) stroke-like conditions. Whole-cell patch clamp electrophysiology combined with simultaneous fluorescence lifetime imaging (FLIM) of the dye...
Neuronal swelling during cytotoxic edema is triggered by Na+ and Cl− entry Ca2+ independent. However, the causes of neuronal death are unknown. Here, we investigate role large-conductance Pannexin-1 (Panx1) channels in edema. Panx1 channel inhibitors reduce delay voltage-gated with veratridine. downstream production reactive oxygen species (ROS) that opens channels. We confirm ROS activates currents whole-cell electrophysiology find scavenging neuroprotective. opening subsequent ATP release...
It is unknown whether neurons can dynamically control the capacity for secretion by promptly changing number of plasma membrane voltage-gated Ca 2+ channels. To address this, we studied peptide release from bag cell Aplysia californica , which initiate reproduction secreting hormone during an afterdischarge. This burst engages protein kinase C (PKC) to trigger insertion a covert channel, Apl v 2, alongside basal 1. The significance 2 recruitment remains undetermined; therefore, used...
Although the contribution of Ca 2+ buffering systems can vary between neuronal types and cellular compartments, it is unknown whether distinct sources within a neuron have different buffers. As individual separate functions, we propose that each handled by unique systems. Using Aplysia californica bag cell neurons, which initiate reproduction through an afterdischarge involving multiple -dependent processes, investigated role endoplasmic reticulum (ER) mitochondrial sequestration, as well...
Electrical transmission is a dynamically regulated form of communication and key to synchronizing neuronal activity. The bag cell neurons Aplysia are group electrically coupled neuroendocrine cells that initiate ovulation by secreting egg-laying hormone during prolonged period synchronous firing called the afterdischarge. Accompanying afterdischarge an increase in intracellular Ca2+ activation protein kinase C (PKC). We used whole recording from paired cultured demonstrate electrical...
After Ca(2+) influx, mitochondria can sequester and subsequently release it back into the cytosol. This form of Ca(2+)-induced (CICR) prolongs signaling potentially mediate activity-dependent plasticity. As is required for its subsequent release, removal systems, like plasma membrane Ca(2+)-ATPase (PMCA), could impact CICR. Here we examine such a role PMCA in bag cell neurons Aplysia californica CICR triggered these during an afterdischarge implicated sustaining excitability peptide...
Microgliosis and astrogliosis characteristically occur at Aβ plaques in the brains of Alzheimer's disease (AD) patients although impact gliosis AD is poorly understood. We studied Aβ-induced using human induced pluripotent stem cell (hiPSC)-derived 3D neurospheres (hiNS), containing only astrocytes neurons versus hiNS with addition iPSC-derived microglia (hiMG). Applying to triggered pathological features including plaque-like aggregates, reactive astrocytes, oxidative stress, neuronal...