RRC ID 46757
Author Turrel O, Lampin-Saint-Amaux A, Préat T, Goguel V.
Title Drosophila Neprilysins Are Involved in Middle-Term and Long-Term Memory.
Journal J. Neurosci.
Abstract UNLABELLED:Neprilysins are type II metalloproteinases known to degrade and inactivate a number of small peptides. Neprilysins in particular are the major amyloid-β peptide-degrading enzymes. In mouse models of Alzheimer's disease, neprilysin overexpression improves learning and memory deficits, whereas neprilysin deficiency aggravates the behavioral phenotypes. However, whether these enzymes are involved in memory in nonpathological conditions is an open question. Drosophila melanogaster is a well suited model system with which to address this issue. Several memory phases have been characterized in this organism and the neuronal circuits involved are well described. The fly genome contains five neprilysin-encoding genes, four of which are expressed in the adult. Using conditional RNA interference, we show here that all four neprilysins are involved in middle-term and long-term memory. Strikingly, all four are required in a single pair of neurons, the dorsal paired medial (DPM) neurons that broadly innervate the mushroom bodies (MBs), the center of olfactory memory. Neprilysins are also required in the MB, reflecting the functional relationship between the DPM neurons and the MB, a circuit believed to stabilize memories. Together, our data establish a role for neprilysins in two specific memory phases and further show that DPM neurons play a critical role in the proper targeting of neuropeptides involved in these processes.
SIGNIFICANCE STATEMENT:Neprilysins are endopeptidases known to degrade a number of small peptides. Neprilysin research has essentially focused on their role in Alzheimer's disease and heart failure. Here, we use Drosophila melanogaster to study whether neprilysins are involved in memory. Drosophila can form several types of olfactory memory and the neuronal structures involved are well described. Four neprilysin genes are expressed in adult Drosophila Using conditional RNA interference, we show that all four are specifically involved in middle-term memory (MTM) and long-term memory (LTM) and that their expression is required in the mushroom bodies and also in a single pair of closely connected neurons. The data show that these two neurons play a critical role in targeting neuropeptides essential for MTM and LTM.
Volume 36(37)
Pages 9535-46
Published 2016-9-14
DOI 10.1523/JNEUROSCI.3730-15.2016
PII 36/37/9535
PMID 27629706
MeSH Animals Animals, Genetically Modified Avoidance Learning / physiology Drosophila Drosophila Proteins / genetics Drosophila Proteins / metabolism Gene Expression Regulation / genetics Maze Learning / physiology Memory / physiology* Mushroom Bodies / cytology* Mushroom Bodies / metabolism Neprilysin / genetics Neprilysin / metabolism* Nerve Net / physiology* Neurons / metabolism* RNA Interference / physiology RNA, Messenger / metabolism Smell / genetics Statistics, Nonparametric Time Factors
IF 5.971
Times Cited 2
Drosophila 9565-R1