My laboratory is interested in the molecular mechanisms underlying learning and memory. We have developed a novel technique to label the cells that encode individual memories in the brains of mice and are able to indelibly tag these neurons using fluorescent molecules (ArcCreERT2 mice). Using these mice, we have shown how a number of conditions affect memory traces in the hippocampus, specifically in the dentate gyrus and CA3 subregions. Moreover, we have been able to optogenetically inhibit these cells and show their necessity for memory expression.
Currently, we are using these mice to investigate what happens to hippocampal memory traces in normal, aged, stressed, depressed, or Alzheimer’s diseased mice. By combining this unique murine line with disease models and optogenetic reporter lines, we hope to identify the altered memory circuits in these conditions and how to manipulate them in order to improve memory retrieval. We hope that these studies might halt, or even reverse, memory loss in these disease states.
In a second line of research, we have begun to develop prophylactics against stress-induced depressive-like behavior. We are interested in understanding how rapid-acting antidepressants, such as ketamine, are able to improve mood. Ketamine has been shown to have rapid-acting and long-lasting effects in rodents and humans following stressful situations. Interestingly, we have found that if given before a stressor or as a prophylactic, we are able to protect against the development of deleterious behavior. We have identified a number of conditions in which ketamine improves behavior and are interested in identifying the molecular mechanisms by which ketamine improves mood. Current studies are aimed at utilizing ketamine in conjunction with our ArcCreERT2 murine line.