Lynn Raymond

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.

Featured Research:

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.