Molecular Genetics of Learning and Memory Formation
Office Phone: (608) 262-5014
Our goal is to understand nervous system function, at the molecular level, during complex behavior. There are three broad areas of interest:
1. Animals can be trained in behavioral tasks, and the resulting memory can be divided into various phases based on pharmacological, genetic and behavioral criteria. We are interested in a cellular and molecular description of what signaling events distinguish the different phases of memory. Of special interest are the molecular events that distinguish memory after repetitive massed training from memory after repetitive spaced training.
2. In all animals, the longest lasting phase of memory, long-term memory, requires acute gene expression around the time of training. This requirement for transcription and translation raises the issue of synaptic specificity: how does the neuron only strengthen the recently active synapse, when transcription and translation are activated? The solution to this cell biological dilemma will require the coordinated use of genetics, cell biology, molecular biology, imaging, biochemistry and behavior. This problem has also led us to an interest in the molecular basis of psychiatric dysfunctions that have attention-based components to the disease.
3. How can memories persist for periods of time much longer than the half-lives of most proteins and protein structures? If “use it or lose it” applies to the persistence of memory, as it seemingly does to synaptic plasticity, how and when do neurons “re-play” experiences? A third goal is to understand the basis for memory persistence that might involve other complex neuronal processes like sleep and circadian rhythms.
Our basic approach involves transgenic manipulation of genes followed by behavioral, cellular and molecular analyses.
- Horiuchi, J.,W. Zhiang, H. Zhou, P. Wu, and J.C.P. Yin. 2004. Phosphorylation inhibits DNA binding of the dCREB2 protein. J. Biol. Chem. 279: 12117-12225.
- Drier, E.A., M. Cowan, M.K. Tello, P. Wu, N. Blace, T.C. Sacktor, and J.C.P. Yin. 2002. Memory enhancement and formation by atypical PKM activity in Drosophila melanogaster. Nat. Neurosci. 5: 316-324.
- Belvin, M.P., H. Zhou, and J.C.P. Yin.1999. The Drosophila dCREB2 gene encodes a component of the circa-dian clock. Neuron 22: 777-787.
- Yin, J.C.P., M. Del Vecchio, H. Zhou, and T. Tully. 1995. CREB as a memory modulator: Induced expression ofa dCREB2 activator isoform enhances long-term memory in Drosophila. Cell 81: 107-115.
- Yin, J.C.P., J.S. Wallach, M. Del Vecchio, E.L. Wilder, W.G. Quinn, and T. Tully. 1994. Induction of a dominant-negative CREB transgene specifically blocks long-term memory in Drosophila. Cell 79: 49-58.