Use It or Lose It

Science Signaling  31 Mar 2009:
Vol. 2, Issue 64, pp. ec113
DOI: 10.1126/scisignal.264ec113

In the olfactory bulb of Drosophila melanogaster, neural activity is not required for the development of circuits, but it is required for their maintenance and modification in the adult. Chiang et al. used the fly olfactory sensory system as a model for exploring the mechanism by which activity protects against neuronal degeneration in established circuits. Olfactory sensory neurons (OSNs) from adult flies lacking Or83b [an odorant receptor and channel required for both evoked and spontaneous action potentials (APs) in a subset of OSNs] developed normally but showed morphological signs of axonal degeneration, such as membrane blebbing, within a few days after the adult emerged from the puparium. Inhibiting APs in OSNs by genetically blocking synaptic vesicle recycling or by expressing tetanus toxin or Kir2.1, which encodes a potassium channel, caused similar neurodegeneration in a cell-autonomous manner. Because glycogen synthase kinase-3β (Gsk-3β), which participates in Wnt signaling, has been implicated in neurodegeneration and long-term potentiation in mammals, the authors investigated the effect of Gsk-3β on inactivity-induced neurodegeneration. They found that expressing a dominant-negative form of gsk-3β protected or83b mutant neurons from degeneration, whereas expressing a constitutively activated form in OSNs induced neurodegeneration. Neural activity increased the amount of the Wnt ligand Wingless (Wg) present in the olfactory bulb, and a series of experiments with activated and dominant-negative forms of Wnt pathway components showed that signaling from Wg through Dishevelled (Dsh) to Gsk-3β protected inactive neurons from degeneration, whereas inhibiting Wnt signaling induced degeneration. This study suggests that neural activity and Wnt signaling, each of which has been separately implicated in maintenance of neuronal circuits, may be mechanistically coupled.

A. Chiang, R. Priya, M. Ramaswami, K. VijayRaghavan, V. Rodrigues, Neuronal activity and Wnt signaling act through Gsk3-β to regulate axonal integrity in mature Drosophila olfactory sensory neurons. Development 136, 1273–1282 (2009). [PubMed]