title: A new genetic model of activity-induced Ras signaling dependent pre-synaptic plasticity in Drosophila.
abstract: Techniques to induce activity-dependent neuronal plasticity in vivo allow the underlying signaling pathways to be studied in their biological context. Here, we demonstrate activity-induced plasticity at neuromuscular synapses of Drosophila double mutant for comatose (an NSF mutant) and Kum (a SERCA mutant), and present an analysis of the underlying signaling pathways. comt; Kum (CK) double mutants exhibit increased locomotor activity under normal culture conditions, concomitant with a larger neuromuscular junction synapse and stably elevated evoked transmitter release. The observed enhancements of synaptic size and transmitter release in CK mutants are completely abrogated by: a) reduced activity of motor neurons; b) attenuation of the Ras/ERK signaling cascade; or c) inhibition of the transcription factors Fos and CREB. All of which restrict synaptic properties to near wild type levels. Together, these results document neural activity-dependent plasticity of motor synapses in CK animals that requires Ras/ERK signaling and normal transcriptional activity of Fos and CREB. Further, novel in vivo reporters of neuronal Ras activation and Fos transcription also confirm increased signaling through a Ras/AP-1 pathway in motor neurons of CK animals, consistent with results from our genetic experiments. Thus, this study: a) provides a robust system in which to study activity-induced synaptic plasticity in vivo; b) establishes a causal link between neural activity, Ras signaling, transcriptional regulation and pre-synaptic plasticity in glutamatergic motor neurons of Drosophila larvae; and c) presents novel, genetically encoded reporters for Ras and AP-1 dependent signaling pathways in Drosophila.
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30022, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Freeman
authors.forename: Mallory
authors.initials: M
authors.lastname: Bowers
authors.forename: Alysia Vrailas
authors.initials: AV
authors.lastname: Mortimer
authors.forename: Christina
authors.initials: C
authors.lastname: Timmerman
authors.forename: Stephanie
authors.initials: S
authors.lastname: Roux
authors.forename: Mani
authors.initials: M
authors.lastname: Ramaswami
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Sanyal
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D003128:Coma / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D023421:Models, Animal; D009469:Neuromuscular Junction / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D018808:Transcription Factor AP-1; C435749:kay protein, Drosophila; D050882:CREB-Binding Protein; D018631:ras Proteins