Our memories are what make us individuals and give meaning to our lives. For this reason, neurological diseases that disrupt memory have devastating consequences to the individual and friends and family. But before we can develop therapies for such diseases, we need to better understand how the brain normally forms and stores memories. This is no small feat– the human brain is comprised of ~90 billion neurons (the primary computational unit of the brain). Each neuron contains perhaps 10,000 proteins and many connections (synapses) with other neurons. One estimate suggests that there are more than 100 trillion synapses in the human brain! The formation and expression of long-term memory (LTM) requires complex interplay between gene products, synapses, neurons, and distributed cellular networks. The long-term goals of my research program are to: (i) determine how gene expression activated during learning modifies and stabilizes the neuronal ensembles involved in LTM storage, and (ii) gain insight into the dynamic cell network interactions critical for the encoding, storing, and retrieval of memory representations. To achieve these goals, we use a cross disciplinary approach, integrating multiple levels of focus including systems-, behavioral-, and molecular neuroscience. These experiments employ a number of technical approaches such as gene expression analysis and profiling, neural activity mapping, neuropharmacological manipulation, local molecular genetic intervention via viral vectors, and a wide range of behavioral paradigms. The cornerstone of this approach is the assertion that a detailed understanding of learning-driven changes in gene expression will both allow insight into the synaptic and cellular bases of memory and also provide a means to probe or manipulate higher-order neural systems critical for cognitive processes in higher animals. In addition to our past and ongoing work focused on understanding fundamental molecular and cellular mechanisms of learning and memory, we have recently begun studies into how interactions between the immune and nervous systems influence higher order cognitive function. Together, findings from this broader research program will allow integration of cutting-edge findings into key neurobiological pathways supporting memory with an understanding of how these pathways are impacted by neurological disease and brain insult.