Grant: Project Grant

An experience changes the brain and leaves a trace behind that underlies our ability to remember. The goal of my lab is to understand the trace at the molecular level. Neurons are connected to other neurons by synapses. Memories are stored by increasing the strength of these connections. We propose that a specialized synapse, molecular distinct from other synapses store the memories. Our goal is to identify the molecules that define this synapse. Remarkably, these synapses are less stable than other synapses and can be specifically erased by inhibitors of a critical molecule required for the maintenance of memories, a protein kinase called PKM. We can use this fact to identify these specialized synapses. Much of our work is done in the simple model of the marine mollusk Aplysia, because in this system the synaptic connections that hold the memory trace have been identified and one can study the molecular traces in neuronal cultures of these neurons. Using novel ways of imaging the synapses as the memories are made and erased, we will determine if the specialized synapses are new synapses formed by learning, or old synapses remodeled by learning. We will test candidates for molecules that define this synapse. We will also study this hypothesis in rodents, where genetics can be used to determine if the molecules identified in Aplysia are required specifically for memory maintenance. Understanding how memories are formed has important health implications both for pathological conditions such as post-traumatic stress disorders and addiction as well as physiological conditions such as aging. A better understanding of how memories are maintained is important for developing strategies for improving memory in both healthy and diseased populations.