Assistant Professor, Biological Sciences
Memory, which refers to the ability of organisms to integrate, encode, store, and recall information, is a complex yet fundamental and adaptive process that defines our experience. At a neurobiological level, multiple forms of information are encoded by changes in the strength of connections between brain cells at highly-specialized sites of communication called synapses. Excitatory synapses are typically housed at small protrusions emanating along neuronal dendrites called dendritic spines, and changes in both structure of dendritic spines and the molecular composition of synapses, termed synaptic plasticity, are thought to serve as the neurobiological basis of learning and memory formation.
While recent discoveries have revealed some of the molecular mechanisms underlying learning and memory consolidation in the brain, there remain fundamental processes that are poorly understood. Neurological disorders affecting memory impact approximately 1.2 million Canadians, affecting autonomy, sense of self, and quality of life for themselves and their families. Care of patients diagnosed with neurodegenerative and neurodevelopmental disease states associated with memory impairments has been estimated to cost the health care system in Canada $10 billion dollars a year, and is predicted to increase to $16.6 billion per year by 2031. Understanding the neurobiological mechanisms that underlie typical memory formation and consolidation is necessary to develop treatments for pathophysiological states characterized by perturbation of memory function, such as Alzheimer’s disease (AD) and Autism Spectrum Disorder (ASD).
Many of the underlying events that regulate synaptic plasticity show a striking similarity to processes that occur during neural development. The molecular mechanisms responsible for neural development can also contribute to plasticity events related to learning and memory in the adult nervous system. Guidance cue proteins are highly-conserved proteins that were first described helping to direct axonal migration and synaptic connections during embryonic development, but continue to play a role in shaping synaptic transmission in the adult brain.
Broadly, our lab focuses on understanding how guidance cues and other neuromodulatory elements can impact synaptic transmission and plasticity underlying spatial memory formation in the adult mammalian hippocampus.
Glasgow, S. D., Ruthazer, E. S., & Kennedy, T. E. (2021) Guiding synaptic plasticity: novel roles for netrin-1 in synaptic plasticity and memory formation in the adult brain. Journal of Physiology. 599 (2) 493-505.
Glasgow, S. D., Wong, E. W., Thompson-Steckel, G., Séguéla, P., Ruthazer, E. S., & Kennedy, T. E. (2020) Pre- and post-synaptic roles for DCC in memory consolidation in the adult mouse hippocampus. Molecular Brain. 13 (56) 1-20.
Glasgow, S. D., McPhedrain, R., Madranges, J. F., Kennedy, T. E., & Ruthazer, E. S. (2019) Approaches and limitations in the investigation of synaptic transmission and plasticity. Frontiers in Synaptic Neuroscience. 11 (20) 1-16. https://www.frontiersin.org/articles/10.3389/fnsyn.2019.00020/full
Wong, E. W.*, Glasgow, S. D.*, Trigiani, L. J., Chitsaz, D., Rymar, V., Sadikot, A., Ruthazer, E. S., Hamel, E., & Kennedy, T. E. (2019) Spatial memory formation requires netrin-1 expression by neurons in the adult mammalian brain. Learning and Memory. 26 (3), 77-83. http://learnmem.cshlp.org/content/26/3/77.full.pdf
Glasgow, S. D., Labrecque, S., Beamish, I. V., Aufmkolk, S., Gibon, J., Han, D., Harris, S. N., Wiseman, P. W., McKinney, R. A., Séguéla, P., De Koninck, P., Ruthazer, E. S., & Kennedy, T. E. (2018) Activity-dependent netrin-1 secretion drives synaptic insertion of GluA1-containing AMPA receptors in the hippocampus. Cell Reports. 25 (1), 168-182.e6 https://www.sciencedirect.com/science/article/pii/S221112471831458X
Boyce, R., Glasgow, S. D., Williams, S., & Adamantidis, A. R. (2016) Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation. Science. 352 (6287), 812-816. https://www.science.org/doi/abs/10.1126/science.aad5252
Munz, M., Gobert, D., Higenell, V., Van Horn, M. R., Glasgow S. D., Schohl, A., & Ruthazer, E. S. (2014) Using two-photon intravital imaging to study developmental plasticity of neural circuits. Microscopy and Microanalysis. 20 (S3), 1342-1343. https://www.cambridge.org/core/journals/microscopy-and-microanalysis/article/using-twophoton-intravital-imaging-to-study-developmental-plasticity-of-neural-circuits/2A50F0791B3D1CF12E2530620BEC3F49
Goldman, J., Ashour, M., Magdesian, M., Tritsch, N., Christofi, N., Chemali, R., Stern, Y., Thompson-Steckel, G., Harris, S., Gris, P., Glasgow, S. D., Grutter, P., Bouchard, J-F., Ruthazer, E. S., Stellwagen, D., & Kennedy, T. E. (2013) Netrin-1 promotes excitatory synaptogenesis between cortical neurons by initiating synapse assembly. Journal of Neuroscience. 33 (44), 17278-89. https://www.jneurosci.org/content/jneuro/33/44/17278.full.pdf
Jego, S., Glasgow, S. D., Gutierrez-Herrara, C., Ekstrand, M., Reed, S. J., Boyce, R., Friedman, J., Burdakov, D., & Adamantidis, A. R. (2013). Optogenetic identification of a rapid-eye movement (REM) sleep modulatory circuit in the hypothalamus. Nature Neuroscience. 16 (11): 1637-43. https://www.nature.com/articles/nn.3522
Horn, K. E., Glasgow, S. D., Gobert, D., Bull, S. J., Luk, T., Girgis, J., Tremblay, M. E., McEachern, D., Bouchard, J. F., Haber, M., Hamel, E., Krimpenfort, P., Murai, K. K., Berns, A., Doucet, G., Chapman, C. A., Ruthazer, E. S., Kennedy, T. E. (2013). DCC expression by neurons regulates synaptic plasticity in the adult brain. Cell Reports. 3: 173-185. https://www.sciencedirect.com/science/article/pii/S2211124712004299