title: Visual Working Memory Requires Permissive and Instructive NO/cGMP Signaling at Presynapses in the Drosophila Central Brain.
abstract: The gaseous second messenger nitric oxide (NO) has been shown to regulate memory formation by activating retrograde signaling cascades from post- to presynapse that involve cyclic guanosine monophosphate (cGMP) production to induce synaptic plasticity and transcriptional changes. In this study, we analyzed the role of NO in the formation of a visual working memory that lasts only a few seconds. This memory is encoded in a subset of ring neurons that form the ellipsoid body in the Drosophila brain. Using genetic and pharmacological manipulations, we show that NO signaling is required for cGMP-mediated CREB activation, leading to the expression of competence factors like the synaptic homer protein. Interestingly, this cell-autonomous function can also be fulfilled by hydrogen sulfide (H2S) through a converging pathway, revealing for the first time that endogenously produced H2S has a role in memory processes. Notably, the NO synthase is strictly localized to the axonal output branches of the ring neurons, and this localization seems to be necessary for a second, phasic role of NO signaling. We provide evidence for a model where NO modulates the opening of cGMP-regulated cation channels to encode a short-term memory trace. Local production of NO/cGMP in restricted branches of ring neurons seems to represent the engram for objects, and comparing signal levels between individual ring neurons is used to orient the fly during search behavior. Due to its short half-life, NO seems to be a uniquely suited second messenger to encode working memories that have to be restricted in their duration.
authors.affiliation: Institut für Zoologie III (Neurobiologie), Johannes Gutenberg-Universität Mainz, Colonel-Kleinmann-Weg 2, 55099 Mainz, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Kuntz
authors.affiliation: Institut für Zoologie III (Neurobiologie), Johannes Gutenberg-Universität Mainz, Colonel-Kleinmann-Weg 2, 55099 Mainz, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Poeck
authors.affiliation: Institut für Zoologie III (Neurobiologie), Johannes Gutenberg-Universität Mainz, Colonel-Kleinmann-Weg 2, 55099 Mainz, Germany. Electronic address: rstrauss@uni-mainz.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Strauss
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D006862:Hydrogen Sulfide / Q000378:metabolism; D008570:Memory, Short-Term / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014796:Visual Perception / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C488977:Mrtf protein, Drosophila; D018377:Neurotransmitter Agents; D009687:Nuclear Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; C419504:bs protein, Drosophila; D009569:Nitric Oxide; D006152:Cyclic GMP; D006862:Hydrogen Sulfide
keywords: CREB; Drosophila; cGMP-regulated cation channels; central complex; hydrogen sulfide; nitic oxide; visual orientation; working memory