THE PRIMARY GOAL OF OUR RESEARCH IS TO UNCOVER THE MOLECULAR AND CELLULAR MECHANISMS UNDERLYING THE FORMATION AND STORAGE OF LONG-TERM MEMORY. WE ALSO STUDY THE MECHANISMS BY WHICH MEMORY RETRIEVAL MODIFIES MEMORIES.

This knowledge is fundamental for generating new hypotheses on the causes of memory impairments in a variety of diseases.

The process of long-term memory formation requires time and the cooperation of multiple cell types in the brain regions of the relevant memory systems. We study the hippocampus-dependent memory system, which processes information of episodic, spatial, contextual, and social memories. A new episodic representation is initially labile and needs to undergo a series of biological processes in the hippocampus-dependent memory system in order to be stably stored. These biological processes include molecular and cellular changes at posttranslational, translational, and transcriptional levels, in a number of cell types, and in different brain regions, and are necessary for stabilizing the initially fragile memory. The process of stabilization of the initially fragile memory is known as memory consolidation. Once consolidated the memory is stable; however, it can become temporarily fragile again if it is recalled. In fact, in some cases, though not always, memory recall temporarily returns the memory to a labile state, and, during this temporal window, the memory re-stabilizes, a process known as reconsolidation. Molecular and cellular mechanisms at the posttranslational, translational, and transcriptional levels are also necessary for the re-stabilization process after recall.

Why is it important that we understand the biology underlying memory consolidation and reconsolidation? These windows of memory fragility offer opportunities for changing memory strength. Identifying molecules and pathways of consolidation and reconsolidation provides critical novel information for developing tools and strategies to strengthen or weaken memories. These approaches could be used in therapies that aim to reverse memory loss such as those associated with cognitive impairments including age-related memory loss, Alzheimer’s disease, and other forms of dementia. They can also be used to develop methods to weaken memories that are overly strong, such as those associated with traumas (post-traumatic stress disorder) or the effects of substance abuse.

We are currently focusing on three major goals:

1. Our studies have shown that some identified gene expression cascades are universal features of long-term memory and are evolutionarily conserved. Among the identified pathways, one became a strong focus of our current studies. We discovered that insulin-like growth factor 2 (IGF-2 or IGF-II) is required for memory consolidation. Moreover, if IGF-2 is administered with learning or memory retrieval, it significantly enhances memory strength and persistence. IGF-2 also reverses age-related memory loss and most core symptoms of autism spectrum disorder and neurodevelopmental disabilities in lab models, suggesting that IGF-2 and its receptor IGF-2R could represent novel targets for developing effective treatments for several psychopathologies. Our current goal is to understand the mechanisms by which IGF-2 and IGF-2R enhance memories and reverse many symptoms in neurodevelopmental disorders and neurodegenerative diseases.