Synapses are the essential point of contact between neurons and their targets for the directional flow of information in the nervous system. The study of how synapses form and how they function is fundamental to our understanding of nervous system connectivity and communication. It is now believed that deficiencies in synaptic function are central to many psychiatric and neurodegenerative diseases such as schizophrenia, Alzheimer’s, Parkinson’s and Huntington’s disease. Thus, it is anticipated that a better understanding of the molecular mechanisms that control these highly specialized structures holds great promise for the development of urgently needed, novel therapies for these diseases.
The principle research objective of my laboratory is to elucidate the cellular and molecular mechanisms underlying the formation, stability, and elimination of CNS synapses. We primarily utilize cultured hippocampal neurons as a model system, and extend these studies to genetically modified mouse models when appropriate. Fundamental questions addressed in the lab include; 1) how does cell-cell contact result in the assembly of pre- and postsynaptic compartments, 2) what are the contributions of pre- and postsynaptic elements to the integrity of the synapse, 3) what are the transsynaptic signals that regulate synaptic plasticity, and 4) is synapse elimination a stereotypical process and, if so, what is the sequence of molecular events underlying synapse disassembly?
Answers to these questions will not only reveal mechanisms underlying developmental and neurodegenerative disorders, but will also provide insight into the molecular signals involved in synaptic strengthening, a process believed essential for learning and memory.
Neuroscience, Synapse Behavior, Cognition, Neurodegenerative and
UBC Student/Postdoctoral Supervision
Principal Supervisor Riki Dingwall, Bachelor’s
Start Date: 2014/9
Principal Supervisor Jordan Shimell, Bachelor’s
Start Date: 2014/1
Principal Supervisor Rachel Gomm, Master’s Thesis
Start Date: 2013/9
Principal Supervisor Wicks Nadine, Post-doctorate
Start Date: 2012/4
Project Description: Localization of Synaptic Proteins
Principal Supervisor Globa Andrea, Doctorate
Start Date: 2011/9
Project Description: Role of Beta-Catenin Stabilization in the Neural Circuitry of
Principal Supervisor Petoukov Eugenia, Master’s Thesis
Start Date: 2009/9
Project Description: Progranulin and TDP-43 Function in Neuronal Connectivity
Principal Supervisor Aiga Mytyl, Master’s Thesis
Start Date: 2008/9
Project Description: Functional Interactions Between Neuroligins and N-cadherin in
Principal Supervisor Stefano Brigidi Gian, Doctorate
Start Date: 2008/1
Project Description: The Role of Delta-Catenin Palmitoylation in Synaptic Plasticity
Principal Supervisor Mills Fergil, Doctorate
Start Date: 2007/9
Project Description: The Role of Beta-Catenin Stabilization in Synaptic Plasticity
Principal Supervisor Sun Yu, Doctorate
Start Date: 2006/9
Project Description: The Role of Cadherin/Beta-catenin in Localizating Synaptic
Vesicles to Synapses
Principal Supervisor Tapia Lucia, Post-doctorate
Start Date: 2006/1
Project Description: Role of Progranulin in Synapse Development and Plasticity
Principal Supervisor Levinson Joshua, Doctorate
Start Date: 2004/9
Project Description: Mecahnisms Regulating Neuroligin Localization at Synapses
2007/7 – 2012/7 New Investigator
Canadian Institutes of Health Research
2006/7 – 2012/7 Career Investigator Award
Michael Smith Foundation for Health Research
2005/10 – 2010/10 Salary Award, TULA Foundation
- Mills F, Bartlett TE, Dissing-Olesen L, Wisniewska MB, Kuznicki J, Macvicar BA, Wang YT, Bamji SX.(2014). Cognitive flexibility and long-term depression (LTD) are impaired following β-catenin stabilization in vivo. Proc Natl Acad Sci U S A. 111(23): 8631-6.
- Brigidi GS, Sun Y, Beccano-Kelly D, Pitman K, Mobasser M, Borgland SL, Milnerwood AJ, Bamji SX. (2014). Palmitoylation of δ-catenin by DHHC5 mediates activity-induced synapse plasticity. Nat Neurosci. 17(4): 522-32.
- Petoukhov E , Fernando S , Mills F , Shivji F , Hunter D , Krieger C , Silverman MA , Bamji SX. (2013). Activity-dependent secretion of progranulin from synapses. Journal of Cell Science. 126(23): 5412-21.
- Brigidi GS , Bamji SX. (2013). Detection of protein palmitoylation in cultured hippocampal neurons by immunoprecipitation and acyl-biotin exchange (ABE). Journal of Visualized Experiments : JoVE. (72)
- Mehran AE , Templeman NM , Brigidi GS , Lim GE , Chu KY , Hu X , Botezelli JD , Asadi A , Hoffman BG , Kieffer TJ , Bamji SX , Clee SM , Johnson JD. (2012). Hyperinsulinemia drives diet-induced obesity independently of brain insulin production. Cell Metabolism. 16(6): 723-37.
- Sun Y , Bamji SX. (2011). β-Pix modulates actin-mediated recruitment of synaptic vesicles to synapses. The Journal of Neuroscience. 31(47): 17123-33.
- Tapia L , Milnerwood A , Guo A , Mills F , Yoshida E , Vasuta C , Mackenzie IR , Raymond L , Cynader M , Jia W , Bamji SX. (2011). Progranulin deficiency decreases gross neural connectivity but enhances transmission at individual synapses. The Journal of Neuroscience. 31(31): 11123-32.
- Diering GH , Mills F , Bamji SX , Numata M. (2011). Regulation of dendritic spine growth through activity-dependent recruitment of the brain-enriched Na⁺/H⁺ exchanger NHE5.. Molecular Biology of the Cell. 22(13): 2246-57.
- Brigidi GS , Bamji SX. (2011). Cadherin-catenin adhesion complexes at the synapse. Current Opinion in Neurobiology. 21(2): 208-14.
- Aiga M , Levinson JN , Bamji SX. (2011). N-cadherin and neuroligins cooperate to regulate synapse formation in hippocampal cultures. The Journal of Biological Chemistry. 286(1): 851-8.
- Guo A , Tapia L , Bamji SX , Cynader MS , Jia W. (2010). Progranulin deficiency leads to enhanced cell vulnerability and TDP-43 translocation in primary neuronal cultures. Brain Research. 1366: 1-8.
- Levinson JN , Li R , Kang R , Moukhles H , El-Husseini A , Bamji SX. (2010). Postsynaptic scaffolding molecules modulate the localization of neuroligins. Neuroscience. 165(3): 782-93.