Molecular Logic For The Storage and Maintenance Of Long-Term Memory

The long-term goal of my laboratory is to understand the molecular and cellular basis of memory storage and cognitive disorders. At the cellular level there are two hallmarks of long-term memory storage: experience-dependent activation of gene expression in the nucleus, and local activation of translation at specific synapses.

Previously I have demonstrated in Eric Kandel’s laboratory that activation of fast axonal transport in pre- and post- synaptic neurons during learning is another critical component of long-term memory storage. Activation of molecular transport to synapses is a rate limiting step and coordinates nuclear and synaptic processes during memory storage. The transported cargos include organelles, proteins, mRNAs, and noncoding RNAs.

In an effort to learn what gene products are transported in specific neurons in response to activity, how they are transported, how they are stored for later use, and eventually when and how they are utilized at specific synapses during learning and memory storage, my laboratory uses an integrated approach that combines several high throughput techniques such as genomics and proteomics with electrophysiology, biochemistry, and imaging. A comprehensive understanding of transported cargos will help us in elucidating signaling pathways at the synapse and mechanisms underlying synaptic dysfunction. Animal models such as Aplysia and mice are used to tackle these questions at the cellular and systems levels. In addition, we explore these questions using mouse models for cognitive disorders such as Alzheimer’s and Huntington’s disease.