Multilevel Modulation of a Sensory Motor Circuit during C. elegans Sleep and Arousal

Sleep is characterized by behavioral quiescence, homeostasis, increased arousal threshold, and rapid reversibility. Understanding how these properties are encoded by a neuronal circuit has been difficult, and no single molecular or neuronal pathway has been shown to be responsible for the regulation of sleep. Taking advantage of the well-mapped neuronal connections of Caenorhabditis elegans and the sleep-like states in this animal, we demonstrate the changed properties of both sensory neurons and downstream interneurons that mediate sleep and arousal. The ASH sensory neuron displays reduced sensitivity to stimuli in the sleep-like state, and the activity of the corresponding interneurons in ASH's motor circuit becomes asynchronous. Restoration of interneuron synchrony is sufficient for arousal. The multilevel circuit depression revealed provides an elegant strategy to promote a robust decrease in arousal while allowing for rapid reversibility of the sleep state.

[1]  Jerome M. Siegel,et al.  The REM Sleep-Memory Consolidation Hypothesis , 2001, Science.

[2]  M. Labouesse.  [Caenorhabditis elegans]. , 2003, Medecine sciences : M/S.

[3]  S. Brenner,et al.  The structure of the nervous system of the nematode Caenorhabditis elegans. , 1986, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[4]  Steven J. Husson,et al.  Specific Expression of Channelrhodopsin-2 in Single Neurons of Caenorhabditis elegans , 2012, PloS one.

[5]  Sharad Ramanathan,et al.  Optical interrogation of neural circuits in Caenorhabditis elegans , 2009, Nature Methods.

[6]  A. Frand,et al.  LIN-42/PERIOD Controls Cyclical and Developmental Progression of C. elegans Molts , 2011, Current Biology.

[7]  Cori Bargmann,et al.  Microfluidics for in vivo imaging of neuronal and behavioral activity in Caenorhabditis elegans , 2007, Nature Methods.

[8]  Karl Deisseroth,et al.  Optogenetics in Neural Systems , 2011, Neuron.

[9]  R. Metherate,et al.  Synaptic mechanisms and cholinergic regulation in auditory cortex. , 2004, Progress in brain research.

[10]  F. Mauguière,et al.  Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans , 2010, Proceedings of the National Academy of Sciences.

[11]  W. Schafer,et al.  Lateral Facilitation between Primary Mechanosensory Neurons Controls Nose Touch Perception in C. elegans , 2011, Neuron.

[12]  Zhaoyang Feng,et al.  The neural circuits and sensory channels mediating harsh touch sensation in Caenorhabditis elegans. , 2011, Nature communications.

[13]  Paul W Sternberg,et al.  Epidermal growth factor signaling induces behavioral quiescence in Caenorhabditis elegans , 2007, Nature Neuroscience.

[14]  S. Brenner,et al.  The neural circuit for touch sensitivity in Caenorhabditis elegans , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[15]  Cori Bargmann.  Chemosensation in C. elegans. , 2006, WormBook : the online review of C. elegans biology.

[16]  Paul W Sternberg,et al.  Transfer characteristics of a thermosensory synapse in Caenorhabditis elegans , 2011, Proceedings of the National Academy of Sciences.

[17]  E. G. Jones,et al.  Synchrony in the Interconnected Circuitry of the Thalamus and Cerebral Cortex , 2009, Annals of the New York Academy of Sciences.

[18]  H. Bringmann,et al.  Reduced activity of a sensory neuron during a sleep-like state in Caenorhabditis elegans , 2011, Current Biology.

[19]  Johannes J. Letzkus,et al.  A disinhibitory microcircuit for associative fear learning in the auditory cortex , 2011, Nature.

[20]  J. Siegel,et al.  Unearthing the Phylogenetic Roots of Sleep , 2008, Current Biology.

[21]  Ralph J Greenspan,et al.  Activation of EGFR and ERK by rhomboid signaling regulates the consolidation and maintenance of sleep in Drosophila , 2007, Nature Neuroscience.

[22]  R. Metherate,et al.  Nicotinic acetylcholine receptors in sensory cortex. , 2004, Learning & memory.

[23]  Nooreen Dabbish,et al.  GABAergic Synaptic Plasticity during a Developmentally Regulated Sleep-Like State in C. elegans , 2011, The Journal of Neuroscience.

[24]  William R. Schafer,et al.  utomated imaging of neuronal activity in freely behaving Caenorhabditis elegans uliette , 2010 .

[25]  Feng Zhang,et al.  Multimodal fast optical interrogation of neural circuitry , 2007, Nature.

[26]  Dai Fukumura,et al.  In vivo imaging of tumors. , 2010, Cold Spring Harbor protocols.

[27]  Cori Bargmann,et al.  C. elegans Responds to Chemical Repellents by Integrating Sensory Inputs from the Head and the Tail , 2002, Current Biology.

[28]  R. Milo,et al.  Topological generalizations of network motifs. , 2003, Physical review. E, Statistical, nonlinear, and soft matter physics.

[29]  N. Munakata.  [Genetics of Caenorhabditis elegans]. , 1989, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[30]  S. Ward,et al.  Electron microscopical reconstruction of the anterior sensory anatomy of the nematode caenorhabditis elegans , 1975, The Journal of comparative neurology.

[31]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[32]  David M. Raizen,et al.  Lethargus is a Caenorhabditis elegans sleep-like state , 2008, Nature.

[33]  David M. Raizen,et al.  Conservation of sleep: insights from non-mammalian model systems , 2008, Trends in Neurosciences.

[34]  William R Schafer,et al.  Food sensitizes C. elegans avoidance behaviours through acute dopamine signalling , 2011, The EMBO journal.

[35]  L. Avery,et al.  Insulin, cGMP, and TGF-beta signals regulate food intake and quiescence in C. elegans: a model for satiety. , 2008, Cell metabolism.

[36]  R. Kerr,et al.  In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to chemical repellents , 2005, The EMBO journal.

[37]  S. Lockery,et al.  Optogenetic analysis of synaptic transmission in the central nervous system of the nematode Caenorhabditis elegans. , 2011, Nature communications.

[38]  N. Jeon,et al.  Microfluidic culture platform for neuroscience research , 2006, Nature Protocols.