A5078210589- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Memory and Neural Mechanisms
- Receptor Mechanisms and Signaling
- Cellular transport and secretion
- Neural dynamics and brain function
- Genetics and Neurodevelopmental Disorders
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- RNA regulation and disease
- Autism Spectrum Disorder Research
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Advanced Memory and Neural Computing
- Genetics, Aging, and Longevity in Model Organisms
- Congenital heart defects research
- Photoreceptor and optogenetics research
- Endoplasmic Reticulum Stress and Disease
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Anesthesia and Neurotoxicity Research
- Erythrocyte Function and Pathophysiology
- Epigenetics and DNA Methylation
- Fibroblast Growth Factor Research
- Mitochondrial Function and Pathology
- Pluripotent Stem Cells Research
York University
2018-2025
University of British Columbia
2013-2022
Vancouver Coastal Health
2020
University of Alberta
2010-2015
Institut des Sciences Cognitives Marc Jeannerod
2011
Selective synapse development determines how complex neuronal networks in the brain are formed. Complexes of postsynaptic neuroligins and LRRTMs with presynaptic neurexins contribute widely to excitatory development, mutations these gene families increase risk developing psychiatric disorders. We find that LRRTM4 has distinct binding partners, heparan sulfate proteoglycans (HSPGs). HSPGs required mediate synaptogenic activity LRRTM4. shows highly selective expression brain. Within...
Synaptopathies contributing to neurodevelopmental disorders are linked mutations in synaptic organizing molecules, including postsynaptic neuroligins, presynaptic neurexins, and MDGAs, which regulate their interaction. The role of MDGA1 suppressing inhibitory versus excitatory synapses is controversial based on vitro studies. We show that genetic deletion vivo elevates hippocampal CA1 inhibitory, but not excitatory, synapse density transmission. Furthermore, selectively expressed by...
Rationale: The hyperactivity of lateral habenula (LHb) has been implicated in the pathophysiology depression, but regulatory mechanisms inhibitory synapses this context remains unclear. MDGA1 and neuroligin2 (Nlgn2), both regulators synapses, selectively interact LHb. We aimed to investigate if their interaction contributes chronic restrained stress (CRS)-induced depression by modulating synapses. Methods: Transgenic mouse models were established conditional knockout/recover expression or...
The capacity for long-term changes in synaptic efficacy can be altered by prior activity, a process known as “metaplasticity.” Activation of receptors modulatory neurotransmitters trigger downstream signaling cascades that persist beyond initial receptor activation and may thus have metaplastic effects. Because β-adrenergic (β-ARs) strongly enhances the induction potentiation (LTP) hippocampal CA1 region, we examined whether these also had effects on LTP induction. Our results show β-ARs...
Noradrenaline critically modulates the ability of synapses to undergo long-term plasticity on time scales extending well beyond fast synaptic transmission. Noradrenergic signalling through β-adrenergic receptors (β-ARs) enhances memory consolidation and can boost longevity potentiation (LTP). Previous research has shown that stimulation one pathway with a protocol induces persistent, translation-dependent LTP enable induction by subthreshold at second, independent pathway. This...
Silencing of a single gene, FMR1, is linked to highly prevalent form mental retardation, characterized by social and cognitive impairments, known as fragile X syndrome (FXS). The FMR1 gene encodes retardation protein (FMRP), which negatively regulates translation. Knockout Fmr1 in mice results enhanced long-term depression (LTD) induced metabotropic glutamate receptor (mGluR) activation. Despite the evidence implicating FMRP LTD, role potentiation (LTP) less clear. Synaptic strength can be...
LRRTMs are postsynaptic cell adhesion proteins that have region-restricted expression in the brain. To determine their role molecular organization of synapses vivo, we studied synapse development and plasticity hippocampal neuronal circuits mice lacking both Lrrtm1 Lrrtm2 . We found LRRTM1 LRRTM2 regulate density morphological integrity excitatory on CA1 pyramidal neurons developing brain but not essential for these roles mature circuit. Further, they required long-term-potentiation CA3-CA1...
Encoding new information requires dynamic changes in synaptic strength. The brain can boost plasticity through the secretion of neuromodulatory substances, including acetylcholine and noradrenaline. Considerable effort has focused on elucidating how substances alter properties. However, determination potential synergistic interactions between different systems remains incomplete. Previous results indicate that coactivation β-adrenergic cholinergic receptors facilitated conversion STP to LTP...
Abstract Neuromodulators regulate higher‐order cognitive processes including learning and memory through modulation of synaptic transmission plasticity. Norepinephrine is a neuromodulator that secreted throughout the brain in response to novelty or increased arousal, which alters neural circuits by increasing modifiability CNS synapses. activates metabotropic receptors, initiating complex intracellular signalling cascades can promote enduring changes strength long‐term potentiation (LTP). In...
Post-transcriptional mechanisms regulating cell surface synaptic organizing complexes that control the properties of connections in brain circuits are poorly understood. Alternative splicing regulates prototypical complex, neuroligin-neurexin. In contrast to well-studied neuroligin splice site B, little is known about A. We discovered inclusion positively charged A1 insert mouse neuroligin-1 increases its binding heparan sulphate, a modification on neurexin. The neurexin recruitment,...
Abstract Pannexin-1 channels have garnered attention for their implications in neurodevelopment, potentially having a dual role mediating delicate balance between cell death and survival. However, comprehensive understanding of the underlying molecular cellular mechanisms Panx1’s potential protective functions throughout neurodevelopment remains to be determined. Zebrafish larvae with loss Pannexin-1a function were subjected an acute exposure 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine...
Abstract The precise organization of pre- and postsynaptic terminals is crucial for normal synaptic function in the brain. In addition to its canonical role as a neurotrophin-3 receptor tyrosine kinase, TrkC promotes excitatory synapse through interaction with presynaptic receptor-type phosphatase PTPσ. To isolate organizer from receptor, we generated mice carrying point mutations that selectively abolish PTPσ binding. synapses mutant had abnormal vesicle clustering density elongation, more...