Molecular Mechanisms Underlying Enhancements in Hippocampal Learning and Memory


This project advances our prior research on genetically engineered “smart” mice, to reveal the specific changes in gene expression that are caused by memory-enhancing mutations.

Recent molecular and cellular studies with transgenic mice have uncovered several biochemical signaling pathways that are involved in learning and memory. However, most of these studies were based on loss of function experiments. Remarkably, more recent reports have indicated that besides impairing function, certain genetic mutations or transgenic manipulations can actually enhance performance in numerous learning tasks in mice. Mutants with learning and memory enhancements represent a unique tool with which to study the biology of learning and memory, and they are a wonderful entry into the more difficult question concerning the biology of extraordinary creativity. Using a variety of strategies, this project aims to unravel the molecular and cellular mechanisms required for enhancing the acquisition and retention of complex information. An important goal of these studies will be to characterize the interplay between molecular and cellular processes in three interacting memory systems (the hippocampus, amygdala and cortex) in mice with learning enhancements. It is possible that manipulations that affect learning enhancements could result in changes in individual brain regions and in the interaction between brain regions. Such changes may provide insight into the mechanisms by which higher cognitive functions, such as those related to high performance and creative emerge in the brain.

Current status: Project live


Primary Investigator: Alcino Silva, Daniel Geschwind, M.D., Ph.D.