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 study memory at a fundamental level, 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. In this model system the connections between neurons (synapses) that change during memory formation have been identified and one can study those synaptic changes in a simple preparation. Once we define an important molecular trace, we use the rodent system to determine the role of this trace in a vertebrate memory model. In this application, we study how memories are maintained and explore the hypothesis that the connections between neurons that maintain memory ('memory synapses') are fundamentally different than other synapses. We are testing the hypothesis that 'memory synapses' are labile and require persistent maintenance by a set of proteins called PKMs that persistently modify proteins at memory synapses. When these proteins are inhibited, memories are erased. We are studying both how PKMs are formed and how they maintain changes at 'memory synapses'. 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.