The Section of Neurobiology

Research Topics

1. Plasticity
2. Neurodegeneration
3. Glutamate receptors
4. Oxygen free radicals
5. Neuron/silicon interface
6. Estrogen

Research Overview

Mechanisms implicated in long-term synaptic potentiation and depression in hippocampus and other brain regions. My laboratory has been investigating for several years the molecular and cellular mechanisms underlying LTP and LTD phenomena in adult rats and rabbits. We have been using a combination of electrophysiological, neurochemical and neuroanatomical techniques to study the roles of various biochemical processes in regulating short-term as well as long-term changes in synaptic efficacy.

Regulation of glutamate receptors. My laboratory has been studying post-translational mechanisms regulating the properties of the AMPA and NMDA receptors. In particular, we are investigating the mechanisms involved in the maturation, processing, insertion and internalisation of the receptors. We are also evaluating the role of calpain-mediated truncation of the C-terminal domains of certain subunits of the receptors in receptor function and regulation.

Role of oxygen free radicals in central nervous system. As a result of my association with Eukarion, Inc., a small start-up pharmaceutical company in Bedford, MA., my laboratory has been investigating the roles of oxygen free radicals in neurodegenerative phenomena. In particular, we have tested the protective effects of a new class of synthetic catalytic scavengers of reactive oxygen intermediates on neuronal damage elicited by excitotoxins, neurotoxins, and beta-amyloid peptides.

Mechanisms underlying selective neuronal degeneration. My laboratory is interested in studying the role of calcium-dependent proteases, calpains, in neuronal degeneration resulting from neuronal insults or injury. Using a combination of pharmacology and mutant mice expressing deletion of calpain genes or mutation of the gene for the endogenous calpain inhibitor, calpastatin, we are evaluating their contribution to neuronal death in various models of neurodegeneration, including models of ischemia and Parkinson's disease.

Additional projects. My laboratory is also involved in several program projects:

* Estrogen and Alzheimer's disease: under this program project, my laboratory is investigating the mechanisms underlying the potential neuroprotective of estrogen and related steroids in Alzheimer's disease.
* Neural tissue/silicon chips interfaces: in collaboration with Dr. Ted Berger, my laboratory is evaluating new technologies to record/stimulate neuronal activity of large ensemble of neurons.

Selected Publications

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Bi R, Rong Y, Bernard A, Khrestchatisky M, Baudry M. (2000) Src-mediated tyrosine phosphorylation of NR2 subunits of NMDA receptors protects from calpain-mediated truncation of their C-terminal domains. J Biol Chem. 275:26477-26483. -PubMed

Bi, R., Foy, M. R., Vouimba, R.-M., Thompson, R.F. and Baudry, M. (2001) Cyclic changes in estrogen regulate synaptic plasticity through the MAP kinase pathway. Proc. Nat. Acad. Sci. 98: 13391:13395. -PubMed

Liu, R., Liu, Y., Bi, X., Thompson, R.F., Doctrow, S.R., Malfroy, B. and Baudry, M. (2003) Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase.catalase mimetics. Proc. Nat. Acad. Sci. 100: 8527-8531. -PubMed

Jourdi, H., Lu, X., Yanagihara, T., Martinez, U., Liu, J., Lauterborn, J., Bi, X., Gall, C., Lynch, G. and Baudry, M. (2005) Ampakine-mediated AMPA receptor down-regulation via calpain-induced PDZ protein truncation in cultured hippocampal slices. J. Pharm. Exp. Therap. 314: 16-26.

Grammer, M., Kuchay, S., Chishti, A. and Baudry, M. (2005) Lack of phenotype for LTP and fear conditioning learning in calpain I knock-out mice. Neurobiol. Learning and Memory. 84: 222-227. -PubMed

Zhou M, Baudry M. (2006) Developmental changes in NMDA neurotoxicity reflect developmental changes in subunit composition of NMDA receptors. J Neurosci. 26(11):2956-63. -PubMed

Ure J, Baudry M, Perassolo M. (2006) Metabotropic glutamate receptors and epilepsy. J Neurol Sci. 247(1):1-9. -PubMed

Dominguez R, Liu R, Baudry M. (2007) 17-beta-Estradiol-mediated activation of extracellular-signal regulated kinase, phosphatidylinositol 3-kinase/protein kinase B-Akt and N-methyl-d-aspartate receptor phosphorylation in cortical synaptoneurosomes. J Neurochem. 101(1):232-40. -PubMed

Xu W, Wong TP, Chery N, Gaertner T, Wang YT, Baudry M. (2007) Calpain-mediated mGluR1alpha truncation: a key step in excitotoxicity. Neuron. 53(3):399-412. -PubMed