Austen Milnerwood, PhD
Austen Milnerwood’s research centers on cell biological, electrophysiological and optical investigation of neural development, connectivity, transmission and plasticity. With a major focus on the early pathophysiology of adult-onset diseases such as movement disorders and dementia, his laboratory aims to develop neuroprotective treatments. Our projects include behavioural studies in rodents, electrophysiology and cell biology in acute brain slices, primary neuronal co-cultures and patient stem cell-derived neuron models.
A strong theme has emerged from studying several proteins harbouring mutations that are autosomal dominantly linked to Parkinson’s disease, in other words, genes transmitted down the family line that are highly predictive for developing PD. There are several proteins that cause “familial PD,” e.g. LRRK2, VPS35 and synuclein. Milnerwood's laboratory is finding that these proteins are involved in the same cellular functions. By learning more about what these proteins are supposed to do and what goes wrong with the mutations present, Milnerwood hopes to work out the common neuronal dysfunction of many forms of parkinsonism and then develop appropriate treatments.
Working out how neuronal function goes awry early in disease states can help to intervene and possibly to prevent the onset or progression of degenerative processes. The world’s population is aging. By 2025, half of the population may be over 60 years old, and up to 2% might have Alzheimer’s or Parkinson’s disease. There is a pressing societal and financial need to learn more about, and to better treat, human neurodegenerative disease.
Austen Milnerwood is always looking to recruit talented and enthusiastic individuals at all levels, austen.milnerwood [at] mcgill.ca (please contact) for details regarding current opportunities
picture adapted from a figure in "Front. Cell. Neurosci. | doi: 10.3389/fncel.2021.569031 "Chronic and acute manipulation of cortical glutamate transmission induces structural and synaptic changes in co-cultured striatal neurons."
Volpicelli-Daley LA, Abdelmotilib H, Liu Z, Stoyka L, Daher JP, Milnerwood AJ, Unni VK, Hirst WD, Yue Z, Zhao HT, Fraser K, Kennedy RE, West AB.(2016) G2019S-LRRK2 Expression Augments α-Synuclein Sequestration into Inclusions in Neurons. J Neurosci.
Volta M., Cataldi, S., Beccano-Kelly D.A., Munsie L.N., Tatarnikov I., Chou P., Bergeron S., Mitchell E., Lim R., Khinda, J., Lloret A., Bennett C.F., Paradiso C., Morari M., Farrer M.J. & Milnerwood A.J. (2015) Chronic and acute LRRK2 silencing has no long-term behavioral effects, whereas wild-type and mutant LRRK2 overexpression induce motor and cognitive deficits and altered regulation of dopamine release. Parkin. & Rel. dis.
Volta M, Milnerwood AJ, Farrer MJ. (2015) Insights from late-onset familial parkinsonism on the pathogenesis of idiopathic Parkinson's disease. Lancet Neurol.
Beccano-Kelly D.A., Volta M., Munsie L.N., Paschall S. A., Tatarnikov I., Co K., Chou P., Cao L.P., Bergeron S., Mitchell E., Han H., Melrose H.L., Tapia L., Raymond L.A., Farrer M.J. & Milnerwood A.J. (2015) LRRK2 overexpression alters presynaptic glutamatergic plasticity, striatal dopamine tone, postsynaptic signal transduction, behavioral activity and long-term memory. Hum Mol Gen.
Munsie L.N., Milnerwood A.J., Seibler, P. Beccano-Kelly D.A., Tatarnikov I.T., Kindah, J., Volta M., Kadgien C., Cao L.P., Tapia L. Klein C. & Farrer M.J. (2015) Retromer-dependent neurotransmitter receptor trafficking to synapses is altered by the Parkinson’s Disease VPS35 mutation p.D620N. Hum Mol Gen.
Beccano-Kelly D.A., Kuhlmann, N., Tatarnikov I., Volta M., Munsie L.N., Chou P., Cao L.P., Han H., Tapia L.,Farrer M.J. & Milnerwood A.J. (2014) Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice. Front. Cell. Neurosci.
Brigidi G.S., Sun Y., Beccano-Kelly D.A., Pitman K., Borgland S.L., Milnerwood A.J. & Bamji S.X. Delta-catenin Palmitoylation is Essential for Activity-dependent Enhancements of Synapse Structure and Efficacy (2014). Nat Neurosci.
Milnerwood A. J., Parsons M., Young F., Singaraja, R., Volta M., Bergeron S., Hayden, M.R. & Raymond, L. A. (2013) Cognitive deficits and severe disruption of synaptic transmission and plasticity in HIP14 palmitoyl transferase knock-out mice. PNAS
Milnerwood A.J., *Kaufman A.M., Sepers M., Gladding C.M., Fan, J., Coquinco, A., Zhang L.Y., Wang L., Qoi J., Lee H., Cynader, M. & Raymond L.A. (2012) Mitigation of augmented extrasynaptic NMDAR signaling and apoptosis in cortico-striatal co-cultures from Huntington’s disease mice.Neurobiol Dis.
Kaufman A.M., *Milnerwood A.J., Sepers M., Coquinco A., She K., Wang L., Lee H., Craig A.M., Cynader M. & Raymond L.A. (2012) Opposing roles of synaptic and extrasynaptic NMDA receptor signaling in striatal and cortical neurons. J. Neurosci.
Petkau T., Neal S.J., Milnerwood A. J., Mew A., Hill A.M., Orban P., Gregg J., Lu H., Feldman H.H., Mackenzie I.R.A., Raymond L.A. & Leavitt B.R. (2012). Synaptic dysfunction in progranulin-deficient mice. Neurobiol.Dis.
Tapia L., Milnerwood A. J., Guo A., Mills F., Yoshida E., Vasuta O.C, Mackenzie I., Raymond, L. A., Cynader M., Jia W., Bamji S.X. (2011). PGRN Deficiency Decreases Neural Connectivity But Enhances Synaptic Transmission at Individual Synapses. J. Neurosci.
Raymond LA, André VM, Cepeda C, Gladding CM, Milnerwood AJ, Levine MS. (2011) Pathophysiology of Huntington's disease: time-dependent alterations in synaptic and receptor function. Neuroscience.
Milnerwood A. J. , Gladding C. M., Pouladi M. A., Kaufman A.M., Hines R. M., Boyd J., Ko R.W.Y., Vasuta O. C., Graham R. K., Hayden M. R., Murphy T. H. & Raymond L. A. (2010). Early increase in extrasynaptic NMDA receptor signalling and expression contributes to phenotype onset in Huntington's disease mice. Neuron
Milnerwood A. J. & Raymond L. A. (2010). Early Synaptic Pathophysiology in Neurodegeneration: Insights from Huntington’s disease. Trends in Neurosciences
Milnerwood A. J. & Raymond, L. A. (2007). Corticostriatal Synaptic Function in Mouse Models of Huntington's Disease: Early Effects of Huntingtin Repeat Length and Protein Load. J. Physiol.
Cummings D. M., Milnerwood A. J., Dallérac G.M., Vatsavayai S. C., Hirst M. C. & Murphy, K. P. (2007). Abnormal cortical synaptic plasticity in mice transgenic for human Huntington's disease mutation. Brain. Res. Bull.
Milnerwood A. J., Cummings D. M., Dallérac G.M., Brown J. Y., Vatsavayai S. C., Hirst M. C., Rezaie P. & Murphy, K. P. (2006). Early development of aberrant synaptic plasticity in a mouse model of Huntington’s disease. Hum. Mol. Gen.