Dr Patricio Opazo

Personal profile

• 2021 - Present: Group Leader, UK Dementia Research Institute, University of Edinburgh
• 2016 - 2020: Group Leader, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
• 2013 - 2015: Postdoctoral Research Fellow, Max Planck Institute of Neurobiology, Munich, Germany
• 2007 - 2012: Postdoctoral Research Fellow, Interdisciplinary Institute for Neuroscience, Université de Bordeaux, France
• 2001 - 2006: PhD, University of California, Los Angeles, US

Research Theme

• Synapses/Circuits/Behaviour 
• Ageing/Degeneration

Research

One of the most puzzling aspects of Alzheimer’s disease (AD) is that the accumulation of amyloid and tau pathology precedes the onset of clinical dementia by several decades. We believe that this delay corresponds to compensatory mechanisms implemented at all levels: first, at the synaptic level following synapse loss, and then at the neuronal and circuit level - and that the saturation of all these compensatory mechanisms mark the onset of clinical dementia.

Given that synaptic plasticity plays a central role in normal cognition as well as in the cognitive deficits associated to AD, our research programme aims to determine whether synaptic repair and compensation is critical to tolerate pathology in AD and thus, whether it may serve as the basis for cognitive resilience and future therapeutic opportunities.

Main objectives and research goals:

1. Investigate the synaptic compensatory and repair events triggered by the loss of synapses in Alzheimer’s disease models

2. Identify the molecular mechanisms underlying synaptic compensation and repair using RNA-seq and proteomic approaches

3. Boost synaptic compensatory and repair mechanisms to delay the onset of cognitive decline in Alzheimer’s disease animal models

Funding

• UK DRI founding partners: Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK

Collaborations

• Dr Daniel Choquet (Université de Bordeaux)
• Dr Victor Anggono (University of Queensland)
• Prof Colin Smith (University of Edinburgh)
• Dr Jenna Gregory (University of Edinburgh)
• Dr Cara Croft (UCL)

Lab Members

Recruiting at present

Publications

Anggono V. and Opazo P., (2022) Editorial: Special issue on The making of memories. Seminars in Cell and Developmental Biology. In press

Choquet, D. and Opazo, P. (2022) The role of AMPAR lateral diffusion in memory. Seminars in Cell and Developmental Biology. In press

Ribeiro LF, Catarino T, Carvalho M, Cortes L, Santos SD, Opazo P, Ribeiro LR, Oliveiros B, Choquet D, Esteban JA, Peça J, Carvalho AL. Ligand-independent activity of the ghrelin receptor modulates AMPA receptor trafficking and supports memory formation. Science Signaling 2021, 14:1953

Delgado, J.Y., Fink, A.E., Grant, S.G.N., O'Dell, T., and Opazo, P. (2018). Rapid homeostatic downregulation of LTP by extrasynaptic GluN2B receptors. Journal of Neurophysiology, 120 (5), 2351-2357.

Opazo, P., Viana da Silva, S., Carta, M., Breillat, C., Coultrap, S.J., Grillo-Bosch, D. et al. (2018). CaMKII Metaplasticity Drives Abeta Oligomer-Mediated Synaptotoxicity. Cell Rep 23, 3137-3145.

Hafner, A.S., Penn, A.C., Grillo-Bosch, D., Retailleau, N., Poujol, C., Philippat, A.,… Opazo., P* and Choquet, D*. (2015). Lengthening of the Stargazin Cytoplasmic Tail Increases Synaptic Transmission by Promoting Interaction to Deeper Domains of PSD-95. Neuron 86, 475-489. *Co-last and co-corresponding.

Carta M, Opazo P, Veran J, Athané A, Choquet D, Coussen F, Mulle C. CaMKII- dependent phosphorylation of GluK5 mediates plasticity of kainite receptors. EMBO J. 2013, 32:496

Opazo P, Sainlos M, Choquet D. Regulation of AMPA receptor surface diffusion by PSD- 95 slots. Current Opinion Neurobiology 2011, 22:1-8

Opazo P and Choquet D. A three-step model for the synaptic recruitment of AMPA receptors. Mol. Cell. Neurosci. 2011, 46(1):1-8

Opazo, P., Labrecque, S., Tigaret, C.M., Frouin, A., Wiseman, P.W., De Koninck, P., and Choquet, D. (2010). CaMKII triggers the diffusional trapping of surface AMPARs through phosphorylation of stargazin. Neuron 67, 239-252

Information for students:

Willingness to discuss research projects with undergraduate and postgraduate students: YES - please click here