Gabriela Popescu

  GABRIELA POPESCU, Ph.D.
  Assistant Professor

  email: popescu@buffalo.edu

  link: Lab Home Page

Molecular Physiology of NMDA Receptors

We investigate molecular mechanisms that control NMDA receptor responses and search for new strategies and means to rationally modify specific functions of this allosteric protein. To understand how endogenous and therapeutic agents alter responses from NMDA receptors in different brain regions and neural environments we are currently using kinetic analysis of single-channel and population responses to patterned stimulation; computational simulations; and plasticity assays. NMDA receptors mediate fast-synaptic transmission and plasticity in the brain and spinal cord. They participate in fundamental brain functions such as learning, memory and behavior and their dysfunction has been associated with severe pathologies. The challenge is then to develop strategies that specifically correct NMDA receptor dysfunction while maintaining activities necessary for critical brain processes. NMDA receptor modulators hold great promise for the prevention and treatment of abnormal neuronal plasticity (chronic pain, addiction) and pathologic neurodegeneration (stroke, Alzheimer’s, Parkinson, Huntington, ALS).

We have recently demonstrated that NMDA receptors have the ability to discriminate input stimulus frequency in the 10-100 Hz range. Current projects in the laboratory are characterizing in depth this novel property; investigating its modulation; and delineating its impact on frequency-dependent post-synaptic bi-directional plasticity phenomena (LTP/LTD).

KEY WORDS: allosteric modulation; drug effects; electrophysiology; excitatory transmission; excitotoxicity; glutamate receptor; kinetic modeling; NMDA receptor; neurodegeneration; neurotransmitter receptor; patch-clamp; synaptic physiology; synaptic plasticity; synaptic transmission

Kussius CL, Popescu GK (2009) Nat Neurosci. Kinetic basis of partial agonism at NMDA receptors; PMID: 19648915.

Kussius CL, Kaur N, Popescu GK, (2009) Pregnanolone sulfate promotes desensitization of activated NMDA receptors, J Neurosci 29(21):6819-27.PMID: 19474309

Zhang, W, Howe, JR, Popescu, GK (2008) Distinct gating modes determine the biphasic relaxation of NMDA receptor currents Nature Neuroscience Oct 26 2008, DOI: 10.1038/nn.2214

Popescu, G (2005) Principles of N-methyl-D-aspartate receptor allosteric modulation. Mol Pharmacol Oct. 68(4):1148-55

Popescu, G (2005) Mechanism-based targeting of NMDA receptor functions. Cell Mol Life Sci Sep. 62(18):2100-11

Popescu, G, Robert A, Howe JR and Auerbach A, (2004) Reaction mechanism determines the NMDA receptor response to repetitive stimulation, Nature 430(7001): 790-793.

Press release; Buffalo Physician article

Popescu, G. and Auerbach A. (2004) The NMDA receptor gating machine: lessons from single-channels. The Neuroscientist 10 (3):192-198

Popescu, G. and Auerbach, A. (2003) Modal gating of NMDA receptors and the shape of their synaptic. Nature Neuroscience 6(5):476-83.

Featured in TINS: Magleby, KL (2004) Modal gating of NMDA receptors, TINS 27(5), 231-233

Peng, H., Myers, J., Fang, X., Stachowiak, E. K., Maher, P. A., Martins, G. G., Popescu, G., Berezney, R., and Stachowiak, M. K. (2002) Integrative nuclear FGFR1 signaling (INFS) pathway mediates activation of the tyrosine hydroxylase gene by angiotensin II, depolarization and protein kinase C. J Neurochem. 81(3), 506-24

Popescu, G., and Napoli, J. L. (2000) Analysis of rat cytosolic 9-cis-retinol dehydrogenase activity and enzymatic characterization of rat AHHII . Biochim Biophys Acta 1476(1), 43-52

Chai, X., Zhai, Y., Popescu, G., and Napoli, J. L. (1995) Cloning of a cDNA for a second retinol dehydrogenase type II. Expression of its mRNA relative to type I. J Biol Chem. 270(47), 28408-12