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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.
I 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.
Bio:
Dr. 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.