Robert Malenka






		Robert Malenka Title Professor Department Psychiatry and Behavioral Sciences Research Interests Long-lasting changes in synaptic strength are important for the modification of neural circuits by experience. A major goal of my laboratory is to elucidate the molecular events that trigger various forms of synaptic plasticity and the modifications in synaptic proteins that are responsible for the changes in synaptic efficacy. Email malenka@stanford.edu Phone 4-2730 Fax Address MSLS P104 Mail Code: 5485 Faculty Research Description Long-lasting activity-dependent changes in the efficacy of synaptic transmission play an important role in the development of neural circuits and may mediate many forms of learning and memory. Work from my laboratory over the last 10 years has demonstrated that there are a variety of related but mechanistically distinct forms of synaptic plasticity. A major goal of my laboratory is to elucidate both the specific molecular events that are responsible for the triggering of these various forms of synaptic plasticity and the exact modifications in synaptic proteins that are responsible for the observed, long-lasting changes in synaptic efficacy. To accomplish this we use cellular electrophysiological recording techniques to examine synaptic plasticity in a variety of different in vitro preparations including thin slices of various regions of the rodent brain and primary neurons in culture. We also use cell biological and molecular techniques to examine the activity-dependent modulation of neurotransmitter receptors and to express dominant negative forms of various synaptic proteins so that their exact functions can be determined. An additional complementary approach has involved examining synaptic physiology and synaptic plasticity in various mutant mouse lines lacking specific synaptic proteins. A related but independent area of research in my laboratory is the elucidation of the synaptic action of drugs of abuse such as the psychostimulants cocaine and amphetamine. Toward this end, we have developed in vitro slice preparations of the nucleus accumbens and ventral tegmental area, brain regions which are thought to mediate several of the behavioral effects of drugs of abuse. We have characterized a novel form of synaptic plasticity in the nucleus accumbens and have done an extensive pharmacological characterization of the synaptic effects of dopamine, cocaine, and amphetamine. Currently we are examining in more detail the underlying mechanisms of dopamine's actions and determining how chronic treatment with drugs of abuse affect the synaptic responses of nucleus accumbens and ventral tegmental area cells. Because chronic exposure to drugs of abuse elicit long-term adaptive changes in critical neural circuits, it is hoped that the knowledge gained from the work on the molecular mechanisms underlying synaptic plasticity will provide important clues to the molecular mechanisms underlying the development of tolerance, dependence and addiction. Representative Publication(s): Malenka, R.C. and Nicoll, R.A.(1999) Long-term potentiation-A decade of progress? Science 285: 1870-1874. Carroll, R.C., Lissin, D.V., Von Zastrow, M., Nicoll, R.A. and Malenka, R.C. (1999) Rapid redistribution of glutamate receptors contributes to long-term depression in hippocampal cultures. Nature Neuroscience 2:454-460. Lüscher, C., Xia, H., Beattie, E.C., Carroll, R.C., von Zastrow, M., Malenka, R.C. and Nicoll, R.A. (1999) Role of AMPA receptor cycling in synaptic transmission and plasticity. Neuron 24: 649-658. Crair, M.C. and Malenka, R.C. A critical period for long-term potentiation at thalamocortical synapses. (1995) Nature 375: 325-328. Malenka, R.C. (1994)Synaptic plasticity in the hippocampus: LTP and LTD. Cell 78: 535-538. Areas of Study Cellular Neurobiology Membrane Excitability Molecular Neurobiology Developmental Neuroscience SBRC Ph.D.