MD, PhD, FRCPC
Director, Djavad Mowafaghian Centre for Brain Health
Professor, Department of Psychiatry, Faculty of Medicine
Louise A. Brown Chair in Neuroscience
Associate member, Department of Medicine, Division of Neurology
Associate member, Department of Cellular and Physiological Sciences
Dr. Lynn Raymond combines neuroscience research with clinical practice in Neurology. Her lab investigates pathogenic mechanisms of Huntington disease (HD), as well as glutamate receptor structure-function, modulation and signaling. Working with HD mouse models, Dr. Raymond made significant contributions to focusing the field on altered striatal neuronal NMDA-type glutamate receptor (NMDAR) trafficking and excitatory synaptic signaling as central mechanisms of early striatal dysfunction. More recently, her lab has focused on early changes in cortical-striatal and cortical pyramidal glutamatergic synaptic plasticity, which may contribute to impairments in learning and cognitive flexibility, as well as promote selective neuronal degeneration. The lab also developed an automated home-cage system for assessing motor learning, and uses electrophysiological and optogenetic approaches to study cortical and striatal activity in awake behaving mice in vivo to determine circuit changes underlying HD. Dr. Raymond served as President for the Canadian Association for Neuroscience. She is Director of the HD Medical Clinic at UBC and a practicing neurologist. As Site PI of several clinical trials and observational studies, she contributes data to publications on multi-centre studies in HD
Altered synaptic function and signaling in Huntington disease. Synaptic dysfunction is a common early change in neurodegenerative disorders, including Alzheimer, Parkinson and Huntington, that could contribute to eventual neuronal loss. As a monogenic disorder, Huntington disease (HD) is an ideal model to investigate these synaptic and circuit signaling changes. The lab focuses on cortical-striatal synapses, the most vulnerable in HD. A variety of approaches are employed, including cortical-striatal co-cultures, acute brain slice and in vivo electrophysiology and optogenetic imaging, to elucidate mechanisms underlying synaptic alterations and mesoscale changes in circuit function and network connectivity.
Role of NMDA-type glutamate receptor signaling and calcium homeostasis in synaptic function and dysfunction. The synaptic versus extrasynaptic distribution of NMDA receptors is a major determinant of synaptic plasticity and neuronal survival signaling. As well, endoplasmic reticulum calcium stores and regulation of cytoplasmic calcium has been identified as a key factor in synaptic function. The lab studies cellular-molecular mechanisms underlying alterations in these critical processes in the context of synaptic dysfunction in early-stage Huntington disease.
Automated behavioural assessment and drug delivery. Measuring behavioural changes in mice can be confounded by the stress of being removed from the home cage, handled and subjected to performing discrete tasks. To mitigate these confounds, the lab developed an automated, 24/7 lever-pulling-for-water task to assess motor learning and kinematics. The lab also developed an automated system for chronic, daily drug delivery in water, which enables more accurate weight-based dosing and minimal handling. These tools are part of a drug testing platform for therapeutic development in mouse models of a variety of neurological disorders.
Milnerwood AJ, Gladding CM, Pouladi, MA, Kaufman, AM, Hines RM, Boyd JD, Ko RWY, Vasuta OC, Graham RK, Hayden MR, Murphy TH, Raymond LA. (2010) Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice. Cited as a “must read” and rated 4.8 by Faculty 1000: Hilmar Bading: Faculty of 1000 Biology, 8 Feb 2010. Featured in a Preview in Neuron 65:145, 2010
Parsons MP, Vanni M, Woodard C, Kang R, Murphy TH, Raymond LA. (2016) Real-time imaging of glutamate clearance challenges an established view of excitotoxicity in Huntington disease. Commentary in Nature Reviews Neurology.
Woodard CL, Bolaños F, Boyd JD, Silasi G, Murphy TH, Raymond LA. (2017) An Automated Home-Cage System to Assess Learning and Performance of a Skilled Motor Task in a Mouse Model of Huntington's Disease. Highlighted in a feature article published online in Nature Lab Animal.
The lab is seeking graduate students who are keenly interested in synaptic physiology, brain optogenetic imaging, and behavioural assessments in mouse models of neurodegenerative disease. Skills and interest in developing new automated cage technologies for simultaneous brain imaging and behavioural assessments in mice are also welcome.
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