Rob Malenka Laboratory

Long-lasting activity-dependent changes in the efficacy of synaptic transmission play an important role in the development of neural circuits and are thought to mediate many forms of learning and memory. Therefore elucidating the molecular mechanisms by which these changes occur will have profound implications for understanding many important nervous system functions including how future behavior is modified by past experience. Work from my laboratory 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 molecular and cell biological 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 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 are currently using a variety of electrophysiological and biochemical techniques with the hope of determining how acute and chronic exposure to drugs of abuse modify synaptic and circuit function in these brain areas. It is our belief 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