Jerry C.P. Yin
Professor, Departments of Genetics and Neurology
Ph.D. University of Wisconsin- Madison
Molecular Genetics of Learning and Memory Formation
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.
4. During the process of memory consolidation, there are processes that occur in the neurons that are activated during the (early) learning process (“synaptic consolidation”), and ones that occur over time as the memory is solidified (“systems consolidation”). In Drosophila, this results in at least two genetically separable, anatomically distinct memory traces that occur over the first three days after the end of training. dCREB2-responsive transcription is involved during this entire process, presumably contributing to the changes in excitability that are at least partially responsible for alterations in circuit-level firing. This represents a unique opportunity to link molecular, cellular, and systems properties through manipulations of a gene in time and space after the end of training.
Our basic approach involves transgenic manipulation of genes followed by behavioral, cellular and molecular analyses.
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