Memories are made of these — amn-expressing DPM neurons (white) innervating the mushroom bodies. Courtesy of J. Douglas Armstrong, Division of Molecular Genetics, University of Glasgow, UK.

The amnesiac ( amn) gene was identified over 20 years ago in a behavioural screen for Drosophila memory mutants. Flies were tested for their ability to associate a specific odour with an electric shock. Initially, those with a mutation at the amn locus could learn as well as their wild-type counterparts, but they were unable to retain the memory for more than 60 minutes.

Associative olfactory memory is processed in specialized structures of the Drosophila brain known as mushroom bodies (MBs), and several olfactory learning genes are expressed in the MB-intrinsic Kenyon cells. In the 22 November issue of Cell, Waddell et al. demonstrate that the amn gene is an exception to the rule. The amn gene encodes the neuropeptide AMN, which shows some sequence homology to the mammalian pituitary-adenylyl-cyclase-activating peptide ( PACAP). AMN stimulates the cyclic AMP signal transduction pathway, which is important for the memory process in the fly and other species. Waddell et al. showed that AMN is predominantly expressed in two large neurons, the dorsal paired medial (DPM) cells. The DPM cell bodies lie outside the MBs, but their processes form an extensive network of branches that innervate the MB lobes.

To demonstrate that signalling from the DPM cells is important for olfactory memory, the researchers temporarily inactivated neurosecretion in these cells. This manipulation resulted in a phenocopy of the amn mutation. They also showed that re-establishment of amn expression in mutant DPM cells was able to restore memory retention, an effect that could not be replicated by expressing the gene in MB-intrinsic neurons.

Secretion of AMN by the DPM cells is therefore likely to be essential for establishing associative olfactory memory in Drosophila. This is the first demonstration of peptidergic modulation of olfactory learning by neurons projecting to the MBs.