Austen J Milnerwood PhD, Assistant Professor, Translational Neuroscience
Dr Milnerwood is an Assistant Professor with more than 13 years neuroscience research experience. He is a specialist in neuronal transmission and plasticity in the hippocampus, cortex, substantia nigra and striatum of whole animals, acute brain slices and primary neuronal co-cultures of normal and transgenic mouse models. Since his early days as a graduate student at the Open University in Milton Keynes, UK, where he received his Ph.D., Dr. Milnerwood’s work has centered on neuronal information transmission, processing and storage, and the perturbation of such systems produced by human neurodegenerative diseases states.
As Head of CAN’s Translational Neuroscience Programs, Dr. Milnerwood manages and mentors a team of technicians, postdoctoral research fellows and graduate students. He is currently working on several projects:
- The neurobiology of LRRK2: Very little is known about the neuronal function of this important protein. Our experiments probing the effects of deletion and overexpression of this protein in neurones will help us understand what LRRK2 does, in order to understand what goes wrong in LRRK2-Parkinsons Disease.
- Early pathophysiology and intervention strategies in LRRK2 transgenic models of PD: We are using a sophisticated combination of transgenic mice, optogenetic neuronal stimulation, voltammetry, electrophysiology, behavior and microdialysis to probe the earliest negative effects of LRRK2 mutations in the brain. By working out what goes wrong first, we expect to design drug treatments that can prevent the onset and progression of LRRK2 and sporadic PD.
- The neurobiology of VPS35, DNAJC13 and EIF4G1: Similarly to LRRK2, very little is known about the neuronal function of these gene products which we know to cause PD when mutated. By studying them all, we are working out where they converge in neuronal cell functions. Surprisingly, we are finding out that all these proteins, which are mutated in PD, are players in the same cellular pathways. Uncovering the links between them is helping us determine the common causes of PD and work out how to protect cells against the negative effects of PD mutations.
- Synuclein, LRRK2 and Tau: What we know about the brain of LRRK2 PD patients suggest that the same symptoms are produced by different pathology, even though the underlying causes are the same. We are studying Tau and synuclein pathology in LRRK2 mice to see how the overexpression, deletion and mutation of LRRK2 change acutely induced Tau and synuclein disease states. By working out the commonalities between these models we expect to gain insights about the mechanisms that are fundamental to all PD.
- Hyperplasticity in novel neuronal co-culture systems: Morphological plasticity is extensively studied as a physical correlate of activity-dependent changes in neural connectivity and information storage. Most of the literature has focused on excitatory synapses of the hippocampus and cortex and activity-dependent changes in dendritic spine size/shape. We use a co-culture system in which GABAergic striatal medium-spiny neurones (MSNs) are grown with glutamatergic cortical cells. In the absence of glutamate transmission MSNs do not develop spines, but rapidly form them when glutamate signaling is pharmacologically unveiled. This postsynaptic structure is highly dynamic in MSNs and is readily manipulated for the study of molecular and synaptic determinants of neuronal morphological plasticity.
- Excitatory synaptic transmission and maintenance in developing neurones - In collaboration with UBC’s Bamji Lab, we study scaffolding molecules e.g., catenin, that regulate synaptic connectivity and maintenance in hippocampal neurones. These structural proteins enable synapses to form and change through dynamic activity-dependent regulation of post-translational modifications such as palmitoylation.
- Synaptic competition and the molecular basis of activity-dependent plasticity: In collaboration with UBC’s Cynader Lab, we study pre- and postsynaptic plasticity in the context of synaptic competition. Populations of neurones are grown in microfluidic isolation chambers in which they are physically and chemically separated from one another, yet maintain axonal connectivity between populations. This technology allows us to specifically alter the activity patterns of one or more of the populations and investigate the resultant changes in pre- and post synaptic connectivity in target populations.