Alessia Mastrodonato, PhD

My laboratory focuses on uncovering the molecular mechanisms that govern learning and memory. We use a novel technique to label and track the specific neurons that encode individual memories in the brains of mice, enabling us to indelibly tag these memory-encoding cells with fluorescent markers. Using this approach, we have explored how various factors—including stress, age, sex, and pharmacological interventions—affect memory traces in the hippocampus, particularly in the dentate gyrus and CA3 subregions. Furthermore, we have employed viral techniques to manipulate these memory-associated neurons, providing direct evidence of their necessity for memory expression. Our next-generation research aims to propel the field forward by integrating multidisciplinary approaches, allowing us to examine memory at the cellular level and offering a deeper understanding of how memory functions throughout the lifespan.

Currently, we are combining this mouse model with RNA sequencing to investigate how rapid-acting antidepressants, such as ketamine, modulate mood and depressive-like behaviors. Through our research, we have identified key conditions under which ketamine exerts its therapeutic effects, and we are focused on uncovering the molecular mechanisms that underlie its ability to improve mood. Our ongoing studies are particularly interested in how factors such as sex and age interact with ketamine treatment, with a goal of refining therapeutic strategies for diverse populations.

In a second line of research, we are translating our findings from the mouse model to human tissue, with a focus on how inflammatory markers contribute to susceptibility to psychiatric disorders and suicide. We are utilizing the iDISCO (immunolabeling-enabled imaging of solvent-cleared organs) technique, combined with automated confocal imaging, to label multiple antibodies in 3D for analysis of human postmortem brains. This approach enables us to study the role of inflammation in the dorsolateral prefrontal cortex in Major Depressive Disorder (MDD) and suicide with unprecedented single-cell resolution, offering new insights into the molecular underpinnings of these conditions and their treatment.