Grant: Operating Grant

An experience leaves a molecular trace inside neurons and identifying this trace is the goal of my research. We believe that memories are defined by these molecular traces and thus, understanding these traces is critical for our understanding of memory. For example, if the traces encoding short-term memories and long-term memories are made in parallel, one can paradoxically make a long-term memory without a short-term memory. To study memory, we use a simple model system, the marine mollusk Aplysia, because in this system the neurons that hold the memory trace have been identified. Moreover, these neurons can be cultured and the changes that occur during memory can be studied under controlled conditions. This is a valuable model for studying memory formation, as seen by the Nobel Prize awarded to Dr. Eric Kandel in 2000 for his pioneering work in this system. In this application, we study a family of molecules that are important for both generating and in some cases encoding memory traces. This family is called protein kinase C (PKC). PKCs encode memories by adding phosphate residues to molecules that determine how well neurons are connected, regulating the strength of these connections, and thus forming memories. When PKCs are persistently activated, they can encode the memory trace, since changes in synaptic strength are maintained by the active kinase. In this application we will determine the rules by which different experiences activate and/or persistently activate distinct members of the PKC family and thus learn how different types of experience lead to different types of memory traces. 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 individuals.