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 Dr. Malenka's 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 his 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 they 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. They 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.