Short-Term to Long-Term Memory

My research has focused on which proteins are synthesized (and thus what genes are "turned-on") during the consolidation from short-term to long-term memory. The distinction is common to all of us: we remember more of a lecture one hour later (short-term) than one week later (long-term). The difference between a fleeting short-term memory and a more permanent long-term memory is: long-term learning induce gene expression to make new proteins that form new connections between neurons in the brain. We do not know how the neurons make these new connections, nor do we know all the proteins needed in the construction of the connections. It would be very significant to understand or control the brain's ability to "lock-in" new facts, knowledge or skills.

Since my arrival at FSU, I have determined when new proteins are required for long-term taste aversion learning by blocking protein synthesis with specific drugs at different time points. At the critical time point, blockade of protein synthesis induces amnesia for the taste and toxin pairing. My research is now aimed at identifying the specific proteins that are synthesized during the learning. We have gathered evidence for 3 proteins in taste aversion learning: c-Fos and ICER (both regulators of protein synthesis), and spinophilin (a structural protein directly involved in nerve-cell connections). Hundreds or thousands of other genes probably are required even for learning the simple fact that a sweet solution is poisonous. It is an indication of the magnitude of the challenge for neuroscience that identifying 3 genes out of a possible 30,000 is a significant advance.This project has been funded by an R01 grant from the National Institute of Deafness and Other Communication Disorders, specifically by the Chemical Senses (taste and smell) branch because of the focus on central processing of taste.

The medical significance of this research is related to both the natural and pathological formation of taste preferences, aversions, and appetites. Humans undergoing therapies that have toxic side effects (e.g., chemotherapy or radiation therapy) often form conditioned taste aversions that are inconvenient at best, and which ultimately cause wasting. Many diseases, such as cancer, are accompanied by loss of appetite, and patients with psychiatric conditions such as anorexia nervosa often express profound aversions to palatable foods. The neurological mechanisms of these aversions probably overlap with the mechanisms of rodent conditioned taste aversion. More generally, understanding how taste-toxin associations are learned may reveal general neural and molecular mechanisms of memory formation common to many forms of learning.