Ph.D., The University of British Columbia, 2003
Neuroscience; glutamatergic synapse; synaptic plasticity; schizophrenia; depression; rodent models of psychiatric disorders
Dysfunction of glutamatergic synapses is believed to play an important role in the pathogenesis of major psychiatric disorders, including schizophrenia and depression. However, many key questions remain unclear such as: What are the causes of the glutamatergic synapse dysfunction? Where in the brain does this dysfunction occur? How does this result in the behavioral phenotypes? Recent advances in several areas have made it possible to directly address these questions. These include the identification of disease-linked genetic variants, the development of novel techniques to study a specific brain circuit, and the demonstration of the role of synaptic plasticity in adaptive behaviors. We are interested in studying normal synaptic plasticity and disease-related synaptic changes in the brain circuits involved in schizophrenia and depression, with the long-term goal of developing methods that will allow the manipulation of activity in specific brain circuits in order to change disease-related behaviors.
A number of complementing methodologies are being employed including patch-clamp recording and calcium imaging of labeled neurons, two-photon imaging of spine morphology and tagged receptors, in vivo virus injection, RNA interference (RNAi)-based gene silencing, activation of specific axon terminals using light-gated cation channels (ChR2), activation or silencing of specific brain regions using transgenes driven by regional specific promoters, as well as assessment of the behavioral consequences of certain manipulations. We hope these studies will shed light on the mechanisms that link the genetic deficits, synaptic dysfunction, and pathophysiology of major psychiatric disorders.
Selected PublicationsLi, H., Penzo, M., Taniguchi, H., Kopec, C.D., Huang, Z.J., Li, B. 2013. Experience-dependent modification of a central amygdala fear circuit. Nat Neurosci. 16: 332-339.
Li, B., Piriz, J., Mirrione, M., Chung, C., Proulx, C., Schulz, D., Henn, F., and Malinow, R. 2011. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature 470: 535–539.
Li, B., Devidze, N., Barengolts, D., Prostak, N., Sphicas, E., Apicella, A.J., Malinow, R., and Emamian, E.S. 2009. NMDA receptor phosphorylation at a site affected in schizophrenia controls synaptic and behavioral plasticity. J. Neurosci. 29: 11965–11972.
Li, B., Woo, R.S., Mei, L. and Malinow, R. 2007. The neuregulin1 receptor erbB4 controls glutamatergic synapse maturation and plasticity. Neuron 54: 583–597.
Kopec, C.D., Li, B., Wei, W., Boehm, J., and Malinow, R. 2006. Glutamate receptor exocytosis and spine enlargement during chemically induced long-term potentiation. J. Neurosci. 26: 2000–2009.