How is a memory formed in the brain? This has been a long-standing question but only recently have various methodologies allowed us to investigate this problem in molecular detail. The principal focus of our laboratory is the hippocampus, a small, curvy structure embedded deep in the cerebrum. Although small in size, it plays a critical role in memory formation.
At the cellular level, a phenomenon called synaptic plasticity is observed there. Neurons communicate with each other through a structure called the synapse. There, neurotransmitters are released from the presynaptic terminal into the synaptic cleft, ultimately reaching postsynaptic receptors on the soma, dendritic shaft, or dendritic spine. On excitatory dendritic spines, a glutamatergic receptor receives the neurotransmitter and converts this chemical signal into an electrical signal. When a presynaptic terminal is stimulated intensely (mimicking a situation when a subject tries to remember) in an in vitro brain slice preparation, synaptic transmission is enhanced and lasts for hours and days. Since this phenomenon, called long-term potentiation (LTP), was first described almost three decades ago, it has been proposed as a potential cellular correlate of learning and memory. Our laboratory investigates the mechanisms underlying LTP by combining different technologies: we construct recombinant neuronal proteins and express them in neurons using molecular biological techniques. The proteins we are interested in are various glutamate receptors and their binding proteins.
Selected Publications:
Hayashi, Y., Shi, S.-H., Esteban, J. A., Piccini, A., Poncer, J. C., and Malinow, R. (2000). Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction, Science 287, 2262-2267.
Nishi, M., Hinds, H., Lu, H. P., Kawata, M., and Hayashi, Y. (2001). Motoneuron-specific expression of NR3B, a novel NMDA-type glutamate receptor subunit that works in a dominant-negative manner, J neurosci 21, RC185. 1-6.
Shi, S.-H., Hayashi, Y.,
Esteban, J. A., and Malinow, R. (2001) Subunit-specific rules governing AMPA
receptor trafficking to synapses in hippocampal pyramidal neurons, Cell 105,
331-344.
Assistant Professor,
Department of Brain and Cognitive Sciences
Investigator, RIKEN-MIT Neuroscience Research Center
Yasunori Hayashi received
his MD and Ph.D. from the Kyoto University in Japan. After postdoctoral training
at the University of Tokyo and at Cold Spring Harbor, Dr. Hayashi joined the
Picower Center for Learning and Memory at MIT in 2000. He is a recipient of
a Young Investigator Award from the Japanese Pharmacological Society and a
Research Fellowship from the Uehara Memorial Foundation.