radish encodes a phospholipase-A2 and defines a neural circuit involved in anesthesia-resistant memory

Abstract

Background: In both vertebrate and invertebrate animals, anesthetic agents cause retrograde amnesia for recently experienced events. In contrast, older memories are resistant to the same treatments. In Drosophila, anesthesia-resistant memory (ARM) and long-term memory (LTM) are genetically distinct forms of long-lasting memory that exist in parallel for at least a day after training. ARM is disrupted in radish mutants but is normal in transgenic flies overexpressing a CREB repressor transgene. In contrast, LTM is normal in radish mutants but is disrupted in CREB repressor transgenic flies. To date, nothing is known about the molecular, genetic, or cell biological pathways underlying ARM.

Results: Here, we report the molecular identification of radish as a phospholipase-A2, providing the first clue about signaling pathways underlying ARM in any animal. An enhancer-trap allele of radish (C133) reveals expression in a novel anatomical pathway. Transgenic expression of PLA2 under control of C133 restores normal levels of ARM to radish mutants, whereas transient disruption of neural activity in C133 neurons inhibits memory retention. Notably, expression of C133 is not in mushroom bodies, the primary anatomical focus of olfactory memory research in Drosophila.

Conclusions: Identification of radish as a phospholipase-A2 and the neural expression pattern of an enhancer-trap allele significantly broaden our understanding of the biochemistry and anatomy underlying olfactory memory in Drosophila.