Research

Molecules in Memory Formation

We are constantly forming new memories about the things we do, the places we go, and the people we see. Some of these memories are fleeting, while others stay with us for days, weeks, or even years. What is it that makes certain memories last for so long? Dr. Cristina Alberini's lab works to understand the cascade of molecular and cellular changes that are required for us to form long-lasting memories. Our hope is that by understanding the changes that occur in the brain during normal memory formation, we can better design treatments for abnormal conditions such as dementia, where we would want to enhance or boost memory, or anxiety/stress disorders, where we would want to weaken a stressful memory. One molecule we are particularly interested in, and the molecule I have focused on for my thesis work, is called insulin-like growth factor-2 (Igf2) which is in the same family of molecules as insulin. 

To study memory formation, we train rats and mice in a variety of memory tasks to assess how well they learn, and measure molecular changes in the brain at different time intervals following training. We can also inject drugs or other compounds to manipulate the molecular cascades that occur following learning, and assess how these manipulations affect the memory of the animal. We are particularly interested in the hippocampus, which is a region of the brain that is important for forming memories of events ("episodic memories") and spatial orientation. 

With Igf2, we have found that levels of Igf2 increase in the hippocampus following learning, and that if we block this increase in expression of Igf2 in the hippocampus, we block long-term memory formation. Interestingly, if we inject Igf2 into the hippocampus after learning, we can actually enhance the animal’s memory! My work so far has focused on determining which cells in the brain produce Igf2, and whether there is a specific Igf2-producing cell population that is critical for promoting memory formation. This will give additional clues as to what Igf2 is doing in the brain to promote memory formation.

Understanding the molecular changes underlying normal memory formation provides important information for understanding what might be wrong in conditions where memory is abnormal. Igf2 is particularly interesting because of its requirement for normal memory formation, and its ability to improve or enhance memory. Igf2 and the molecular cascades associated with it could potentially be targeted for drug development to help people with poor memory function, such as patients with Alzheimer’s disease.  Promisingly, studies from our lab and other labs using mouse models of disorders such as Alzheimer's disease and autism spectrum disorder have suggested that Igf2 may improve the symptoms of those disorders. Although it will be many years before this work will lead to a memory-boosting drug, we are beginning the first steps into determining the molecular cascades that follow Igf2 expression.

My thesis work, which sought to identify and characterize the cell type(s) involved in Igf2 signaling in memory signaling, was published in Neuron in 2023.