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Matthew Parsons

BioMedical Sciences
PhD Memorial
Assistant Professor of BioMedical Sciences (Neurosciences)

Room H5340A, HSC
Division of BioMedical Sciences
Faculty of Medicine
Memorial University of Newfoundland
St. John's, NL, Canada  A1B 3V6
 
t: 709-864-3373
f: 709-864-6007
lab: 709-864-3369

matthew.parsons@med.mun.ca

Research interest:
 
Glutamate is the most abundant excitatory neurotransmitter in the brain. It is essential for rapid cell-cell communication and can promote brain health by turning on specific cell-survival genes.  Paradoxically, glutamate can also contribute substantially to the death of neurons in a process called excitotoxicity. The clinical relevance of understanding glutamate signaling lies in the well-accepted view that glutamate-mediated excitotoxic cell death occurs in many diseases of the central nervous system. My lab is interested in determining the physiological processes that go awry in disease states that results in a shift in the primary function of glutamate from one that promotes brain health to one that negatively impacts cell communication and survival. Of particular interest is Huntington disease, a genetically inherited neurodegenerative disorder in which much of the cell death has been attributed to the toxic effects of glutamate. For more information on Huntington disease, interested individuals are encouraged to visit http://en.hdbuzz.net/. 
 
Projects focus on two main streams:
 
1. How is glutamate cleared in both health and disease? When glutamate is released from a synapse, it must be removed rapidly from the extracellular space in order to minimize its toxic effect. This is achieved by a family of membrane proteins called glutamate transporters. We are interested in studying the contribution of different transporters to glutamate clearance in different brain regions and how their physiological function may be altered in neurodegenerative diseases including Alzheimer and Huntington disease. 
 
2. How does a dysfunction in glutamate signaling contribute to the cognitive decline associated with neurodegenerative disease? It is well-known that many neurodegenerative conditions are associated with cognitive symptoms such as memory loss. Cognitive function relies heavily on synaptic plasticity - the regulated, activity-dependent changes in the strength of the connections between neurons - which itself is largely dependent upon intact glutamate signaling. Here, we are interested in understanding how alterations in glutamate signaling can ultimately lead to the memory loss associated with neurodegenerative disease. 
 
Techniques:
 
The above research questions are carried out using a combination of optogenetics, electrophysiology and live-imaging, both in situ and in cell culture. This approach employs a combination of older, well-established techniques that have become invaluable to our understanding of the central nervous system, as well as novel techniques that take advantage of the growing list of genetically encoded fluorescent actuators and reporters that enable us to both manipulate and measure brain activity, respectively, through the use of light. These techniques provide an excellent training environment for anyone ranging from undergraduate students looking for experience in a laboratory setting, to postdoctoral fellows seeking to employ optogenetics and electrophysiology to ask clinically-relevant questions related to nervous system function and its dysfunction in disease.
 

Recent relevant peer-reviewed publications:

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. Accepted Feb 2021.
 
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.