Roberto Malinow, M.D., Ph.D., Cold Spring Harbor Laboratory

Please visit the Malinow Lab home page

Synaptic model proposed to explain long-term synaptic potentiation (LTP), a possible cellular substrate of learning and memory. In this model, excitatory synapses have either AMPA receptors (AMPA-R) and NMDA receptors (NMDA-R), or only NMDA receptors. LTP causes postsynaptic activation of protein kinases (PK) and the delivery of AMPA receptors to both types of synapses.

Roberto Malinow
Professor
M.D., New York University, 1984;
Ph.D., University of California, Berkeley, 1986
Neuroscience; synaptic transmission; synaptic plasticity; learning and memory

email malinow@cshl.edu, phone (516) 367-8416, fax (516) 367-8372

We are investigating the biological basis of learning and memory by studying the physiology of synapses in the rodent brain. We manipulate synaptic transmission by expressing recombinant proteins through virally mediated transfection. We monitor transmission with electrophysiological and optical imaging techniques.

The AMPA-type and NMDA-type receptors found at excitatory synapses have different roles in transmission and plasticity. A large fraction of these synapses appear to have only NMDA-type receptors, which render them silent when the postsynaptic cell is at resting membrane potential. Such pure NMDA synapses, as well as AMPA-containing synapses, add AMPA receptors during long-term potentiation (LTP) and development. We are determining the molecular mechanisms by which AMPA receptors and NMDA receptors are delivered to or removed from synapses. We find that the subunit composition of the receptor governs how it traffics to synapses. An increase in synaptic AMPA receptors could be the molecular basis of memory storage. An increase in synaptic NMDA receptors may control the ease with which such modifications take place.

A separate project addresses the role of the Alzheimer’s disease-related protein, amyloid precursor protein (APP), in synaptic transmission. We have evidence that processing of APP is controlled by neural activity. Conversely, APP products have effects on synaptic transmission. These relations produce a negative feedback homeostatic system that, if abrogated, could lead to disease.

Please visit the Malinow Lab home page

Selected Publications

LLi, B., Woo, R.S., Mei L., Malinow, R. 2007. The neuregulin-1 receptor erbB4 controls glutamatergic synapse maturation and plasticity. Neuron 54:583-97.

Hsieh, H., Boehm, J., Sato C., Iwatsubo, T., Tomita T., Sisodia, S., Malinow, R. 2006. AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron 52:831-433.

Rumpel, S., LeDoux, J., Zador, A., and Malinow, R. 2005. Postsynaptic receptor trafficking underlying a form of associative learning. Science 308: 83–88.

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: 331–343.

Hayashi,Y., Shi, S.-H., Esteban, J.A., Piccini, A., Poncer, J.-C., and Malinow, R. 2000. Driving AMPA receptors into synapses by LTP or CaMKII: requirement for GluR1 PDZ domain interaction. Science 287: 2262–2267.