Grant: Operating Grant

An experience changes the brain and leaves a trace behind. This trace is what we call memory. The goal of my lab is to understand the trace at the molecular level. Different experiences lead to different molecular traces that last for different periods of time. Our understanding of memory rests on identifying these molecular traces. We take a reductionist approach to studying memory, identifying the simplest system in which we can examine the memory trace. One model is the marine mollusk Aplysia, because in this system the neurons that hold the memory trace have been identified. This is a valuable system as seen by the Nobel Prize awarded to Dr. Eric Kandel in 2000 for his work on memory in this system. We also use cultures of hippocampal neurons from rats. While the changes induced in this system are not as closely linked to memory as in Aplysia, forms of plasticity that are linked to human diseases such as the Fragile X syndrome can be studied in this system. In this application, we study how protein translation is important for forming the memory trace. An experience leads to increased production of proteins from messenger RNAs that already exist. This is a mechanism to make new proteins quickly and the increased levels of these proteins can then change the strength of synapses, leading to a change in the circuitry of the brain and the memory trace. We study this mechanism at the level of the translational machinery, trying to understand how, in neurons, the translational machinery (the machine that converts messenger RNAs into proteins) is regulated by the stimulations that lead to memory formation. Understanding how memories are formed has important health implications both for pathological conditions such as mental retardation, and physiological conditions such as aging. A better understanding of how memories are formed is important for developing strategies for improving memory in both healthy and diseased populations.