title: Propagation of Homeostatic Sleep Signals by Segregated Synaptic Microcircuits of the Drosophila Mushroom Body.
abstract: The Drosophila mushroom body (MB) is a key associative memory center that has also been implicated in the control of sleep. However, the identity of MB neurons underlying homeostatic sleep regulation, as well as the types of sleep signals generated by specific classes of MB neurons, has remained poorly understood. We recently identified two MB output neuron (MBON) classes whose axons convey sleep control signals from the MB to converge in the same downstream target region: a cholinergic sleep-promoting MBON class and a glutamatergic wake-promoting MBON class. Here, we deploy a combination of neurogenetic, behavioral, and physiological approaches to identify and mechanistically dissect sleep-controlling circuits of the MB. Our studies reveal the existence of two segregated excitatory synaptic microcircuits that propagate homeostatic sleep information from different populations of intrinsic MB "Kenyon cells" (KCs) to specific sleep-regulating MBONs: sleep-promoting KCs increase sleep by preferentially activating the cholinergic MBONs, while wake-promoting KCs decrease sleep by preferentially activating the glutamatergic MBONs. Importantly, activity of the sleep-promoting MB microcircuit is increased by sleep deprivation and is necessary for homeostatic rebound sleep (i.e., the increased sleep that occurs after, and in compensation for, sleep lost during deprivation). These studies reveal for the first time specific functional connections between subsets of KCs and particular MBONs and establish the identity of synaptic microcircuits underlying transmission of homeostatic sleep signals in the MB.
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Sitaraman
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Aso
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Felix
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Rubin
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: michael.nitabach@yale.edu.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Nitabach
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000502:physiology*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D024521:Mushroom Bodies / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D012098:Reproduction / Q000502:physiology; D012890:Sleep / Q000502:physiology*; D012903:Smell / Q000502:physiology; D013329:Structure-Activity Relationship