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X-WR-CALNAME:Djavad Mowafaghian Centre for Brain Health | DMCBH
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X-WR-CALDESC:Events for Djavad Mowafaghian Centre for Brain Health | DMCBH
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SUMMARY:Dr. Jonathan Epp: Resilience and Risk: How Sex Differences in Inhibitory Networks Shape Alzheimer’s Disease Trajectories
DESCRIPTION:Recent work from our lab has focused on understanding the function of the retrosplenial cortex (RSC) in both health and disease. This region plays a critical role in supporting cognitive functions such as memory integration and spatial navigation and is also one of the earliest sites of dysfunction in Alzheimer’s disease. By investigating the cellular and circuit mechanisms underlying RSC activity\, we aim to uncover how vulnerability emerges and how it might be reversed. \nI will present recent findings that converge on a cohesive narrative: intrinsic sex differences in inhibitory circuits shape baseline resilience and set the stage for differential vulnerability to disease. In both Alzheimer’s disease models and human patients\, early dysfunction and loss of PV⁺ interneurons in the RSC lead to circuit instability\, disrupted network dynamics\, and memory deficits. Yet\, this vulnerability is not irreversible. Targeted interventions ranging from circuit-level manipulations to environmental enrichment can restore inhibitory balance and rescue cognitive function. Together\, this work outlines a sex-informed\, circuit-based framework for understanding the earliest stages of Alzheimer’s disease and offers a roadmap for developing more personalized strategies for prevention and intervention. \n  \nBio: \nDr. Jonathan Epp has expertise in microscopy\, histology and behavioural neuroscience. Dr. Epp was hired in 2017 as an Assistant Professor in the Department of Cell Biology and Anatomy and a full member of the HBI at UCalgary. His background in neuroscience was shaped by his training with several world leaders in behavioural neuroscience\, adult neurogenesis and learning and memory. He received his B.Sc. and M.Sc. in neuroscience from the University of Lethbridge\, Canadian Center for Behavioral Neuroscience with Dr. Robert Sutherland\, (1999-2003; 2003-2005) His Ph.D. was completed at the University of British Columbia in 2010 with Dr. Liisa Galea. Dr. Epp conducted postdoctoral work at the Hospital for Sick Children in Toronto with Dr. Paul Frankland where he was the recipient of funding from several sources including the Ontario ministry of research and innovation and was granted a prestigious NARSAD young investigator award from the Brain and behavior research foundation. Dr. Epp has expertise in adult neurogenesis\, structural and functional integration of new neurons and has performed numerous studies examining hippocampal function in both rodent models and in humans. He has recently demonstrated the functional importance of adult neurogenesis in forgetting and how this mechanism protects against memory interference. His current work is focused on examining brain-wide structural and functional connectivity changes that mediate learning\, memory and forgetting. Recently\, Dr. Epp has become a leader in the field of tissue clearing\, a novel research area that has allowed for unique insight into the 3-dimensional organization of intact brain tissue. His recent work has resulted in the development of protocols for tissue clearing and analysis of intact neuronal morphology and brain wide functional networks. Dr. Epp has published extensively with 28 peer-reviewed papers in high impact journals such as Nature communications\, Neuron and Journal of neuroscience.
URL:https://www.centreforbrainhealth.ca/events/dr-jonathan-epp-resilience-and-risk-how-sex-differences-in-inhibitory-networks-shape-alzheimers-disease-trajectories/
LOCATION:DMCBH Room 3402\, 2215 Wesbrook Mall\, Vancouver\, British Columbia\, V6T 1Z3\, Canada
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DTSTART;TZID=America/Vancouver:20250731T130000
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CREATED:20250721T000304Z
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SUMMARY:Dr. Gerald Obermair: Presynaptic α2δ proteins: calcium channels\, synaptic functions\, and pathophysiological roles in neurodevelopmental disorders
DESCRIPTION:We are delighted to host Dr. Gerald Obermair\, a well-known neuroscientist from Karl Landsteiner University\, Krems\, Austria who will be visiting on Thursday\, July 31. \nSeminar summary: \nVoltage-gated calcium channels (VGCCs) are essential regulators of cellular excitability and synaptic communication. Among their auxiliary subunits\, the α2δ proteins play a pivotal role in regulating channel expression\, biophysical properties\, and synaptic functions. Clinically\, α2δ proteins are the target of gabapentinoids\, Gabapentin and Pregabalin\, therapeutics use in the treatment of neuropathic pain\, restless leg syndrome\, epilepsy and generalized anxiety disorder. This presentation focuses on the presynaptic functions of α2δ proteins\, particularly α2δ-2 and α2δ-3\, and presents insights into their role in neurodevelopmental and neuropsychiatric disorders. \nExperimental data from knockout and rescue models reveal that α2δ proteins are key organizers of excitatory glutamatergic synapses\, with highly redundant roles across isoforms. Presynaptic expression of a specific α2δ-2 splice variant modulates postsynaptic GABA receptor abundance and synaptic wiring\, independent of the interaction with calcium channels. Mutations in CACNA2D genes are linked to a spectrum of disorders including epileptic encephalopathy\, autism\, and schizophrenia. Functional analyses of specific mutations (e.g.\, R596P and G303V in α2δ-2) demonstrate altered calcium signaling\, impaired synaptic targeting\, and disrupted trans-synaptic communication. Moreover\, behavioral and electrophysiological studies in α2δ-3 knockout mice further support the role of α2δ proteins in shaping neuronal connectivity and plasticity. \nThese findings underscore the dual role of α2δ proteins in channel-dependent and independent mechanisms\, highlighting their contribution to both channelopathies and synaptopathies. Understanding these pathways offers promising avenues for future therapeutic intervention in neurodevelopmental disorders.
URL:https://www.centreforbrainhealth.ca/events/dr-gerald-obermair-presynaptic-%ce%b12%ce%b4-proteins-calcium-channels-synaptic-functions-and-pathophysiological-roles-in-neurodevelopmental-disorders/
LOCATION:DMCBH Room 3402\, 2215 Wesbrook Mall\, Vancouver\, British Columbia\, V6T 1Z3\, Canada
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