Matthew Parsons

Research Interests

Our lab is broadly focused on glutamate neurotransmission and its role in maintaining synaptic function and brain health. We are particularly interested in how glutamate clearance mechanisms are disrupted in the context of neurodegenerative disease. Much of our work focuses on Huntington’s and Alzheimer’s disease, with an emphasis on understanding how synaptic dysfunction arises in these conditions, how it disrupts neural circuits, and how we might intervene to restore normal synaptic function through novel therapeutic strategies. We use various methodologies to tackle these goals, including:

• Super-resolution imaging to study the nanoscale organization and properties of synaptic and perisynaptic proteins

• Electrophysiology, including whole-cell and field recordings, to assess functional changes in synaptic transmission
• Viral-mediated gene manipulations
• Real-time imaging of fluorescence biosensors
• In vivo and ex vivo models of neurodegenerative disease to link cellular changes with behavioral phenotypes

By targeting these earliest molecular events, we aim to uncover novel strategies to preserve or restore healthy communication between neurons before widespread network failure occurs.

In addition to our disease-focused work, we are deeply interested in the fundamental principles of excitatory neurotransmission. We study how the healthy brain regulates glutamate signaling across different types of synapses, with a focus on the mechanisms that control release, clearance, and receptor organization. This includes exploring the heterogeneity of glutamate dynamics from one synapse to the next, to better understand how fine-tuned synaptic properties support complex neural computations.

Opportunities for Trainees

Please note that all trainee positions (volunteer, honours, MSc, PhD, postdoctoral) are currently filled. Interested individuals can check back in the fall term. Any available positions will be updated here.

Relevant publications (Parsons lab members indicated by *)

J.C. Barron*, L.J. Dawson, M.C. Grace, K.A. Senior, K.C. Ryan, F. Nafar*, J.J. Blundell, M.P. Parsons (2025). Huntingtin plays an essential role in the adult hippocampus. Neurobiology of Disease. Mar:206:106810. doi: 10.1016/j.nbd.2025.106810.

V.F. Monteiro-Cardoso; X.Y. Yeo; H. Bae; D.C. Mayan; M. Wehbe; S. Lee; K. Krishna-K; S.H. Baek; L.F. Palomera; L.H. Wu; L.S. Pakkiri; S. Shanmugam; K.P. Sem; M.G. Yew; M.P. Parsons; M.R. Hayden; L.L.L Yeo; V.K. Sharma; C.L. Drum; E.A. Liehn; S. Sajikumar; S. Davanger; D. Jo; M.Y.Y. Chan; B.Y.Q. Tan; S. Jung; R. Singaraja (2024). The bile acid chenodeoxycholic acid associates with reduced stroke in humans and mice. Journal of Lipid Research. Jan;66(1):100712. doi: 10.1016/j.jlr.2024.100712.

E.P. Hurley*, B. Mukherjee*, L.Z. Fang, J.R. Barnes*, J.C. Barron*, F. Nafar*, M. Hirasawa, M.P. Parsons (2024). GluN3A and Excitatory Glycine Receptors in the Adult Hippocampus. The Journal of Neuroscience. 44 (42) e0401242024

L.Z. Fang, V. Linehan, M. Licursi, C.O. Alberto, J.L. Power, M.P. Parsons, M. Hirasawa (2023). Prostaglandin E2 activates melanin-concentrating hormone neurons to drive diet-induced obesity. Proceedings of the National Academy of Sciences (PNAS USA). Aug;120(31):e2302809120. doi: 10.1073/pnas.2302809120.

K.J. Brymer*, E.P. Hurley*, J.C. Barron*, B. Mukherjee*, J.R. Barnes*, F. Nafar*, M.P. Parsons (2023). Asymmetric dysregulation of glutamate dynamics across the synaptic cleft in a mouse model of Alzheimer's disease. Acta Neuropathologica Communications. 11, 27 (2023). https://doi.org/10.1186/s40478-023-01524-x

J.C. Barron*, E.P. Hurley*, M.P. Parsons (2021). Huntingtin and the synapse. Frontiers in Cellular Neuroscience. June;https://doi.org/10.3389/fncel.2021.689332

A.S. Ravalia*, J.C. Barron*, S.L.M. Purchase*, A.L. Southwell, M.R. Hayden, M.P. Parsons (2021). Super-resolution imaging reveals extrastriatal synaptic dysfunction in presymptomatic Huntington disease mice. Neurobiology of Disease. May;152:105293. doi: 10.1016/j.nbd.2021.105293.

C.M. Wilkie*, J.C. Barron*, K.J. Brymer*, J.R. Barnes*, F. Nafar*, M.P. Parsons (2021). The effect of GLT-1 upregulation of extracellular glutamate dynamics. Frontiers in Cellular Neuroscience. Mar 26;15:661412. doi: 10.3389/fncel.2021.661412.

K.J. Brymer*, J.R. Barnes*, M.P. Parsons (2021). Entering a new era of quantifying glutamate clearance in health and disease. Journal of Neuroscience Research. Jun;99(6):1598-1617. doi: 10.1002/jnr.24810.

M.O. Quartey, J.N.K. Nyarko, J.M. Maley, J.R. Barnes*, M.A.C. Bolanos, R.M. Heistad, K.J. Knudsen, P.R. Pennington, J. Buttigieg, C.E. De Carvalho, S.C. Leary, M.P. Parsons, D.D Mousseau (2021). The Aβ(1-38) peptide is a negative regulator of the Aβ(1-42) peptide implicated in Alzheimer disease progression. Scientific Reports. 11(1):431. doi: 10.1038/s41598-020-80164-w.

C.M. Wilkie*, J.R. Barnes*, C.L. Benson*, K.J. Brymer*, F. Nafar*, M.P. Parsons (2020) Hippocampal synaptic dysfunction in a mouse model of Huntington disease is not alleviated by ceftriaxone treatment. eNeuro. 7(3):ENEURO.0440-19.2020. doi: 10.1523/ENEURO.0440-19.2020.

J.R. Barnes*, B. Mukherjee*, B.C. Rogers*, F. Nafar*, M. Gosse*, M.P. Parsons (2020). The relationship between glutamate dynamics and activity-dependent synaptic plasticity. The Journal of Neuroscience. 40(14): 2793-2807.

V. Linehan, L.Z. Fang, M.P. Parsons, M. Hirasawa (2020) High-fat diet induces time-dependent synaptic plasticity of the lateral hypothalamus. Molecular Metabolism. 36:100977. doi: 10.1016/j.molmet.2020.100977.

J.G. Quirion*, M.P. Parsons (2019). The onset and progression of hippocampal synaptic plasticity deficits in the Q175FDN mouse model of Huntington disease. Frontiers in Cellular Neuroscience. Jul 17;13:326. doi: 10.3389/fncel.2019.00326

N.F. Pinky*, C.W. Wilkie*, J.R. Barnes*, M.P. Parsons (2018). Region- and activity-dependent regulation of extracellular glutamate. The Journal of Neuroscience. 38(23):5351-5366.

A.L. Southwell, H.B. Kordasiewicz, D. Langbehn, N.H. Skotte, M.P. Parsons, E.B. Villanueva, N.S. Caron, M.E. Østergaard, L.M. Anderson, Y. Xie, L.D. Cengio, H. Findlay-Black, C.N. Doty, B. Fitsimmons, E.E. Swayze, P.P. Seth, L.A. Raymond, F. Bennett, M.R. Hayden (2018). Huntingtin suppression restores cognitive function in a mouse model of Huntington’s disease. Science Translational Medicine. 10(461)

S. Sanders, M.P. Parsons, K. Mui, A.L. Southwell, S. Franciosi, D. Cheung, S. Waltl, L.A. Raymond, M.R. Hayden (2016). Sudden death due to paralysis and synaptic and behavioral deficits when Hip14/Zdhhc17 is deleted in adult mice. BMC Biology. 14(1):108.

A.L. Southwell, A. Smith-Dijak, C. Kay, M. Sepers, E.B. Villanueva, M.P. Parsons, Y. Xie, L. Anderson, B. Felczak, S. Waltl, S. Ko, D. Cheung, L. Dal Cengio, R. Slama, E. Petoukhov, L.A. Raymond, M.R Hayden (2016). An enhanced Q175 knock-in mouse model of Huntington disease with higher mutant huntingtin levels and accelerated disease phenotypes. Hum. Mol. Genet. 25(17):3654-3675

M.P. Parsons, M.P. Vanni, R. Kang, C. Woodard, T.H. Murphy, L.A. Raymond (2016). Real-time imaging of glutamate clearance challenges an established view of excitotoxicity in Huntington disease. Nature Communications. 7:11251 doi: 10.1038/ncomms11251.

C. Buren#, M.P. Parsons#, A. Smith-Dijak, L.A. Raymond #Equal Contribution (2016). Impaired development of cortico-striatal synaptic connectivity in a cell culture model of Huntington disease.
Neurobiology of Disease. 87:80-90

C. Buren, G. Tu, M.P. Parsons, M.P. Sepers, L.A. Raymond (2016). Influence of cortical synaptic input on striatal neuronal excitability and sensitivity to excitotoxicity in corticostriatal co-culture. J. Neurophys. 116(2):380-90.

M.P. Parsons and L.A. Raymond (2014). Extrasynaptic NMDA receptor involvement in central nervous system disorders. Neuron. 82(2):279-93 (review)

K. Kolodziejczyk, M.P. Parsons, A.L Southwell, M.R. Hayden, L.A. Raymond (2014). Striatal synaptic dysfunction and hippocampal plasticity deficits in the hu97/18 mouse model of Huntington disease. PloS One. 9(4):e94562

M.P. Parsons, Rujun Kang, Shaun S. Sanders, Michael R. Hayden, Lynn A. Raymond (2014). Bidirectional control of PSD-95 by non-pathologic huntingtin. J. Biol. Chem. 289(6):3518-28

A.J. Milnerwood#, M.P. Parsons#, Fiona B. Young, Roshni Singaraja, Sonia Franciosi, Michael R. Hayden, Lynn A. Raymond (2013). Memory and synaptic deficits in Hip14/DHHC17 knockout mice. Proc. Natl. Acad. Sci. USA 10(50):20296-301 #Equal contribution

Book Chapter:

Parsons MP and Raymond LA. Chapter 21: Huntington Disease. Neurobiology of Brain Disorders. Elsevier. 2015.