By combining theoretical analysis with a reductionist experimental approach, we have uncovered properties of synaptic modification that can, in principle, account for observed experience-dependent changes in cellular responses. We established that synapses throughout the cerebral cortex are bidirectionally modifiable, and that the sign or polarity of the modification depends on the type of NMDA receptor (NMDAR) activation at the time of induction. We also showed that the conditions required to induce long-term synaptic potentiation (LTP) or depression (LTD) vary depending on the history of cellular or synaptic activity, a property now called metaplasticity. The major questions that confront us now are the molecular mechanisms of bidirectional synaptic plasticity and metaplasticity, and, of particular importance, the contributions of these mechanisms to naturally occurring synaptic modifications in the brain. We are employing a wide range of techniques - biochemical, anatomical, electrophysiological, and behavioral -to address these key questions in the hippocampus and visual cortex. The lab has made a key discovery on how synapses are weakened, and this promises to shed light on disorders ranging from mental retardation and autism to Alzheimer's disease.
Frenkel, M.Y. and Bear, M.F. 2004. How monocular deprivation shifts ocular dominance in visual cortex of young mice. Neuron 44: 917-923.
Whitlock, J. R., Heynen, A. J., Shuler, M.G. and Bear, M.F. 2006. Learning induces LTP in the hippocampus. Science 313: 1093-1097.
Dölën, G., Osterweil, E., Shankaranarayana Rao, B.S., Smith, G. B., Auerbach, B.D., Chattarji, S. and Bear, M.F. 2007. Correction of fragile X syndrome in mice. Neuron 56: 955-962.