Memory of invertebrates and vertebrates can be divided into separate phases: short-term and long-term. Long-term memory has for years been experimentally defined by two operational criteria: (1) it is resistant to agents that disrupt normal brain activity such as anesthesia, electroconvulsive shock or concussion, and (2) it requires new protein synthesis for its establishment. Historically, memories that fit these operational definitions were implicitly considered to be two manifestations of the same molecular event. However, analysis of the Drosophila mutant radish has provided strong evidence that the two criteria define two completely separate components of long-term memory. Mutant radish flies show near-normal initial learning in an olfactory learning paradigm, followed by rapid memory decay. The radish mutation virtually abolishes anesthesia-resistant memory (Folkers et al, Proc. Natl. Acad. Sci. USA 90: 8123-8127, 1993). In striking contrast, this mutation has no detectable effect on protein-synthesis dependent memory (Tully et al., Cell 79: 35-47, 1994). These results with radish mutants clearly indicate that long-term memory consists of two distinct components which appear to be independent and additive on performance (ibid). Currently, the only clue to anesthesia-resistant (consolidated) memory is the radish mutatation. The applicant proposes to clone and identify the radish gene. They have mapped this gene to 140 kb interval on the X-chromosome and have cloned the DNA of this interval by chromosomal walking. They have identified eight transcripts representing five to seven genes. They have isolated and sequenced cDNAs representing five of these transcripts. Homology searches have so far revealed one plausible radish candidate, an ABC1 homology. ABC1 proteins are involved in endocytosis, ion transport or both. The applicant will isolate and sequence wild-type and mutant genomic DNA corresponding to the open reading frame of this and other candidate genes. They will compare these sequences in order to detect the mutation in radish. They will then transform radish flies with a wild-type genomic DNA fragment that includes the indicated transcript, and they will assay these transformants for rescue of memory to definitively identify the radish gene. The identification of the radish gene and its biochemical function will provide information about the molecular mechanism underlying anesthesia-resistant component of long-term memory. Anesthesia-resistant memory in Drosophila almost certainly corresponds to consolidated memory (electroconvulsive-shock-resistant memory) in higher animals. This is the most intensely studied form of long-term memory in vertebrates and corresponds directly to memory in humans that is sensitive to concussion and acute trauma.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Neurology C Study Section (NEUC)
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Massachusetts Institute of Technology
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United States
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Folkers, Elisabeth; Waddell, Scott; Quinn, William G (2006) The Drosophila radish gene encodes a protein required for anesthesia-resistant memory. Proc Natl Acad Sci U S A 103:17496-500