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? 

Decades of work have shown that a cascade of changes occur at the cellular and molecular level in the brain when we form long-lasting memories. Understanding the molecular changes underlying normal or typical memory formation provides important information for understanding what might be wrong in conditions where memory is abnormal, such as dementia or stress and anxiety disorders. 

Rodents (rats and mice) are a common laboratory model for studying memory formation. We can train the rats and mice in a variety of memory tasks to assess how well they learn the tasks. We can inject drugs or other compounds to manipulate the typical molecular processes that occur in the brain following learning, and measure how these manipulations affect the memory of the animal. We can also collect brain samples to measure molecular changes (e.g. gene or protein expression) in the brain at different time intervals following training. 

In Dr. Cristina Alberini's laboratory, we focus on a brain area called the hippocampus, which is particularly important for forming memories of events ("episodic memories") and for spatial orientation. One molecule of interest is called insulin-like growth factor-2 (Igf2), which is in the same family of molecules as insulin. Igf2 is an important molecule for growth and development, but it continues to be expressed in select tissues in adults, including in the brain.

Previous work in the Alberini lab showed that levels of Igf2 increase in the hippocampus following learning, and that if we block this increase in Igf2, we block long-term memory formation. Interestingly, if we artificially boost Igf2 levels by injecting Igf2 into the hippocampus after learning, we can actually enhance the animal’s memory! This could have exciting therapeutic implications. Indeed, further work from the Alberini lab and other groups using mouse or rat models of aging, Alzheimer's disease, and even autism spectrum disorder, have suggested that Igf2 may improve the symptoms of those disorders.

In order to further explore the therapeutic potential of Igf2, it is important to understand how naturally produced Igf2 is acting on the brain to promote memory formation. My thesis 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 may give additional clues as to what Igf2 is doing in the brain to promote memory formation. 

Surprisingly, I identified a type of cell called pericytes as the cell-type responsible for the learning-regulated production of Igf2. Pericytes are cells that wrap around blood vessels to regulate blood flow, form the blood-brain barrier, among other functions. This was a surprising finding because previous studies on learning and memory have typically focused on neurons (i.e., the cells that send electrical signals in the brain) or astrocytes (i.e., the "support" cells that interact closely with neurons), and other types of brain cells have largely been ignored. While pericytes have been studied in the context of several neurological diseases, including epilepsy, spinal cord injury, and stroke, their role in normal brain function is understudied. Further work is needed to understand how pericytes and neurons cooperate to promote memory and potentially other brain functions. 

The results of my thesis work was published in Neuron in 2023.