Peter Nguyen (PhD, University of Toronto)
7-14A Medical Sciences Building
University of Alberta
Canada T6G 2H7
Tel: 780 492-8163 (office)
Courses That I Teach:
- PHYSL 212-Introduction to Human Physiology
- PHYSL 372-Systems Neuroscience
- PHYSL 444-Current Topics in Neuroscience (coordinator too)
- NEURO 210-Introduction to Clinical Neuroscience
- PSYCI 511-Biological Aspects of Psychiatry
Collaborators, Past and Present:
- Ted Abel, University of Pennsylvania
- Cliff Abraham, Joanna Williams, University of Otago, New Zealand
- Glen Baker, University of Alberta
- Christos Gkogkas, University of Edinburgh
- Eric Klann, New York University
- Farah Lubin, University of Alabama
- Thomas O’Dell, University of California, Los Angeles
- Nahum Sonenberg, McGill University
- Douglas Wahlsten, University of Alberta
- Yu Tian Wang, University of British Columbia
Synaptic Plasticity in the Mammalian Brain
Neurons can change the physiological strength of transmission at their synapses in response to altered electrical activity. This activity-dependent synaptic plasticity is important for many aspects of brain physiology and cognition, including the construction of neural circuits during brain development, associative learning, and the formation of long-term memories. Impaired synaptic plasticity may contribute to some disorders of mental processes.
There are several types of synaptic plasticity in the mammalian brain. Boosting ("potentiation") and weakening ("depression") of synaptic transmission are two examples of synaptic plasticity. A major challenge facing neuroscientists is to elucidate the mechanisms of these various forms of synaptic plasticity and define their roles in brain function and behaviour. The behaviours of laboratory mice, and the synaptic physiology of neurons in brain structures important for cognition, can be measured to identify which molecules and circuits are critical for specific types of behaviour and synaptic plasticity.
Why study the plasticity of synapses, learning and memory?
Learning is the acquisition of new information, and memory is its retention over time. Much of what we do in the present and future is shaped by our memories of past experiences. It is widely accepted that synaptic plasticity is critical for learning and memory. Failure of synaptic plasticity can impair the formation of new memories. This can decrease quality of life by damaging mental health. Effective treatment of memory impairments will improve quality of life, but it requires basic research aimed at identifying mechanisms and brain circuits underlying memory impairment. Determining how synaptic plasticity occurs will help us better understand how the brain learns, and stores, new information. It will also reveal rational strategies for the treatment of learning deficits and memory dysfunction (e.g. memory loss during Alzheimer disease). Apart from these practical applications, unraveling the mechanisms of synaptic plasticity in the mammalian brain is, by itself, a fun and satisfying endeavour, because it will shed light on the neural mechanisms of behaviour.
What we do in this laboratory?
We study genetically modified and wildtype mice to try to elucidate the roles of specific signalling molecules in synaptic plasticity, learning, and memory. A second objective is to define the mechanisms by which genetic background may influence synaptic physiology, learning, and memory. A third goal is to characterize synaptic plasticity in mouse models of memory impairment.
Population and single-neuron recordings of synaptic plasticity in brain slices; tests of behavioural learning and memory; fear conditioning, social recognition, social transmission of food preferences.
Woo, N.H., and Nguyen, P.V. (2002). “Silent” metaplasticity of the late phase of LTP requires protein phosphatases. Learning & Memory, 9: 202-213. [Highlighted in a commentary in Learning & Memory, 9: 153-155].
Woo, N.H., and Nguyen, P.V. (2003). Protein synthesis is required for synaptic immunity to depotentiation. Journal of Neuroscience, 23: 1125-1132. [Highlighted in a review in Trends in Neurosciences 27: 378-383].
Duffy, S.N., and Nguyen, P.V. (2003). Postsynaptic application of a peptide inhibitor of cyclic AMP-dependent protein kinase blocks expression of long-lasting synaptic potentiation in hippocampal neurons. Journal of Neuroscience, 23: 1142-1150.
Duffy, S.N., Nguyen, P.V., and Baker, G. (2004). Phenylethylidenehydrazine, a novel GABA-transaminase inhibitor, reduces epileptiform activity in rat hippocampal slices. Neuroscience, 126: 423-432.
Young, J.Z., and Nguyen, P.V. (2005). Homosynaptic and heterosynaptic inhibition of synaptic tagging and capture of LTP by previous synaptic activity. Journal of Neuroscience, 25: 7221-7231.
Gelinas, J.N., Banko, J.L., Hou, L., Sonenberg, N., Weeber, E.J., Klann, E., and Nguyen, P.V. (2007). ERK and mTOR signaling couple beta-adrenergic receptors to translation initiation machinery to gate induction of protein synthesis-dependent LTP. Journal of Biological Chemistry, 282: 27527-35.
Tenorio G., Connor S.A., Guevremont D., Abraham W.C., Williams J., O’Dell T.J., and Nguyen P.V. (2010). “Silent” priming of translation-dependent LTP by beta-adrenergic receptors involves phosphorylation and recruitment of AMPA receptors. Learning & Memory, 17: 627-38
Connor S.A., Hoeffer C.A., Klann E., and Nguyen P.V. (2011). Fragile-X mental retardation protein regulates heterosynaptic plasticity in the hippocampus. Learning & Memory, 18: 207-220.
Connor S.A., Wang Y.T., and Nguyen P.V. (2011). Activation of beta-adrenergic receptors facilitates heterosynaptic translation-dependent long-term potentiation. The Journal of Physiology (London), 589(17): 4321-40.
Connor S.A., Roy B., Maity S., Ali D.W., and Nguyen P.V. (2012). Conversion of short-term potentiation to long-term potentiation in mouse CA1 by co-activation of muscarinic and beta-adrenergic receptors. Learning & Memory, 19: 535-542. [On The Cover of Learning & Memory, Dec 2012].
Maity S., Rah S., Sonenberg N., Gkogkas C.G., and Nguyen P.V. (2015). Norepinephrine triggers metaplasticity of LTP by increasing translation of specific mRNAs. Learning & Memory, 22: 499-508 [On The Cover of Learning & Memory, Oct 2015].
Maity S., Jarome T.J., Blair J.P., Lubin F., and Nguyen P.V. (2015). Noradrenaline goes nuclear: Epigenetic modifications during long-lasting synaptic potentiation triggered by activation of beta-adrenergic receptors. The Journal of Physiology (London), 594: 863-881.
Nguyen, P.V., and Gerlai, R.E. (2002). Behavioral and physiological characterization of inbred mouse strains: prospects for elucidating the molecular mechanisms of mammalian learning and memory. Genes, Brain, and Behavior, 1: 72-81.
Nguyen, P.V., Woo, N.H. (2003). Regulation of hippocampal synaptic plasticity by cyclic AMP-dependent protein kinases. Progress in Neurobiology, 71: 401-437.
Josselyn, S.A., and Nguyen, P.V. (2005). CREB, synapses, and memory disorders: Past progress and future challenges. Current Drug Targets – CNS and Neurological Disorders. [Special Issue: Cognitive Therapeutics] 4: 481-497
Nguyen, P.V. (2006). Comparative plasticity of brain synapses in inbred mouse strains. The Journal of Experimental Biology, 209: 2293-2303
Abel, T. and Nguyen, P.V. (2008). Regulation of hippocampus-dependent memory by cyclic AMP-dependent protein kinase. In: The Essence of Memory, Amsterdam: Elsevier; eds. W. Sossin, V. Castellucci, JC Lacaille, S. Belleville. (Progress in Brain Research, 169: 97-115).
O’Dell T.J., Connor S.A., Gelinas J.N., and Nguyen P.V. (2010). Viagra for your synapses: Enhancement of hippocampal long-term potentiation by activation of beta-adrenergic receptors. Cellular Signalling 722: 728-736.
Connor S.A. and Nguyen P.V. (2014). Prescient synapses: gating future neuronal consciousness through synaptic tagging and metaplasticity. In S. Sajikumar (ed.), “Synaptic Tagging and Capture”, pp. 173-196. Springer-Verlag: New York.
O’Dell T.J., Connor S.A., Guglietta R., and Nguyen P.V. (2015). Beta-adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus. Learning & Memory, 22: 461-471.