title: Nonreciprocal homeostatic compensation inDrosophilapotassium channel mutants.
abstract: Homeostatic control of intrinsic excitability is important for long-term regulation of neuronal activity. In conjunction with many other forms of plasticity, intrinsic homeostasis helps neurons maintain stable activity regimes in the face of external input variability and destabilizing genetic mutations. In this study, we report a mechanism by whichDrosophila melanogasterlarval motor neurons stabilize hyperactivity induced by the loss of the delayed rectifying K+channelShaker cognate B(Shab), by upregulating the Ca2+-dependent K+channel encoded by theslowpoke(slo) gene. We also show that loss of SLO does not trigger a reciprocal compensatory upregulation of SHAB, implying that homeostatic signaling pathways utilize compensatory pathways unique to the channel that was mutated. SLO upregulation due to loss of SHAB involves nuclear Ca2+signaling and dCREB, suggesting that theslohomeostatic response is transcriptionally mediated. Examination of the changes in gene expression induced by these mutations suggests that there is not a generic transcriptional response to increased excitability in motor neurons, but that homeostatic compensations are influenced by the identity of the lost conductance.NEW & NOTEWORTHYThe idea that activity-dependent homeostatic plasticity is driven solely by firing has wide credence. In this report we show that homeostatic compensation after loss of an ion channel conductance is tailored to identity of the channel lost, not its properties.
authors.affiliation: Department of Biology, Volen Center for Complex Systems, and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts; and.
authors.forename: Eugene Z
authors.initials: EZ
authors.lastname: Kim
authors.affiliation: Department of Biology, Volen Center for Complex Systems, and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts; and.
authors.forename: Julie
authors.initials: J
authors.lastname: Vienne
authors.affiliation: Department of Biology, Volen Center for Complex Systems, and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts; and.|Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts.
authors.forename: Michael
authors.initials: M
authors.lastname: Rosbash
authors.affiliation: Department of Biology, Volen Center for Complex Systems, and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts; and griffith@brandeis.edu.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Griffith
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005260:Female; D055785:Gene Knockdown Techniques; D006706:Homeostasis / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D007814:Larva; D009046:Motor Neurons / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051669:Shab Potassium Channels / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D002413:Cations, Divalent; D029721:Drosophila Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D012333:RNA, Messenger; D051669:Shab Potassium Channels; C064033:Shab protein, Drosophila; C494844:slo protein, Drosophila; D002118:Calcium
keywords: Drosophila; excitability; homeostasis; ion channel; motor neuron