Enhancement of Odor Avoidance Regulated by Dopamine Signaling in Caenorhabditis elegans

The enhancement of sensory responses after prior exposure to a stimulus is a fundamental mechanism of neural function in animals. Its molecular basis, however, has not been studied in as much depth as the reduction of sensory responses, such as adaptation or habituation. We report here that the avoidance behavior of the nematode Caenorhabditis elegans in response to repellent odors (2-nonanone or 1-octanol) is enhanced rather than reduced after preexposure to the odors. This enhancement effect of preexposure was maintained for at least 1 h after the conditioning. The enhancement of 2-nonanone avoidance was not dependent on the presence or absence of food during conditioning, which generally functions as a strong positive or negative unconditioned stimulus in the animals. These results suggest that the enhancement is acquired as a type of nonassociative learning. In addition, genetic and pharmacological analyses revealed that the enhancement of 2-nonanone avoidance requires dopamine signaling via D2-like dopamine receptor DOP-3, which functions in a pair of RIC interneurons to regulate the enhancement. Because dopamine signaling has been tightly linked with food-related information to modulate various behaviors of C. elegans, it may play different role in the regulation of the enhancement of 2-nonanone avoidance. Thus, our data suggest a new genetic and pharmacological paradigm for nonassociative enhancement of neural responses that is regulated by dopamine signaling.

[1]  M. Chalfie,et al.  The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration , 1991, Nature.

[2]  S. R. Nash,et al.  Dopamine receptors: from structure to function. , 1998, Physiological reviews.

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

[4]  Paul W. Sternberg,et al.  An imaging system for standardized quantitative analysis of C. elegans behavior , 2004, BMC Bioinformatics.

[5]  C M Loer,et al.  Serotonin-deficient mutants and male mating behavior in the nematode Caenorhabditis elegans , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  H. Horvitz,et al.  Effects of starvation and neuroactive drugs on feeding in Caenorhabditis elegans. , 1990, The Journal of experimental zoology.

[7]  Koutarou D. Kimura,et al.  Temperature Sensing by an Olfactory Neuron in a Circuit Controlling Behavior of C. elegans , 2008, Science.

[8]  Cornelia I. Bargmann,et al.  Neuropeptide feedback modifies odor-evoked dynamics in C. elegans olfactory neurons , 2010, Nature Neuroscience.

[9]  G. Esposito,et al.  Efficient and cell specific knock-down of gene function in targeted C. elegans neurons. , 2007, Gene.

[10]  H. Horvitz,et al.  Serotonin and octopamine in the nematode Caenorhabditis elegans. , 1982, Science.

[11]  C. H. Rankin,et al.  Caenorhabditis elegans: A new model system for the study of learning and memory , 1990, Behavioural Brain Research.

[12]  Cori Bargmann,et al.  The Caenorhabditis elegans odr-2 gene encodes a novel Ly-6-related protein required for olfaction. , 2001, Genetics.

[13]  D. van der Kooy,et al.  Dopamine modulates the plasticity of mechanosensory responses in Caenorhabditis elegans , 2004, The EMBO journal.

[14]  J. Waddington,et al.  Drugs acting on brain dopamine receptors: a conceptual re-evaluation five years after the first selective D-1 antagonist. , 1989, Pharmacology & therapeutics.

[15]  C. Wysocki,et al.  Odorant exposure increases olfactory sensitivity: olfactory epithelium is implicated , 2001, Physiology & Behavior.

[16]  Michael R Koelle,et al.  Mechanism of extrasynaptic dopamine signaling in Caenorhabditis elegans , 2004, Nature Neuroscience.

[17]  G. Ruvkun,et al.  Control of Neural Development and Function in a Thermoregulatory Network by the Lim Homeobox Gene Lin-11 , 2022 .

[18]  M. Mizunami,et al.  Roles of octopaminergic and dopaminergic neurons in mediating reward and punishment signals in insect visual learning , 2006, The European journal of neuroscience.

[19]  Cori Bargmann,et al.  A circuit for navigation in Caenorhabditis elegans , 2005 .

[20]  D. van der Kooy,et al.  Olfactory associative learning in Caenorhabditis elegans is impaired in lrn-1 and lrn-2 mutants. , 1999, Behavioral Neuroscience.

[21]  C. Sahley,et al.  What we have learned from the study of learning in the leech. , 1995, Journal of neurobiology.

[22]  C. Wysocki,et al.  Induction of olfactory receptor sensitivity in mice. , 1993, Science.

[23]  Yi Zheng,et al.  Differential Expression of Glutamate Receptor Subunits in the Nervous System of Caenorhabditis elegans and Their Regulation by the Homeodomain Protein UNC-42 , 2001, The Journal of Neuroscience.

[24]  Nektarios Tavernarakis,et al.  A Synaptic Deg/enac Ion Channel Mediates Learning in C. Elegans by Facilitating Dopamine Signalling , 2022 .

[25]  R. Kerr,et al.  In Vivo Imaging of C. elegans Mechanosensory Neurons Demonstrates a Specific Role for the MEC-4 Channel in the Process of Gentle Touch Sensation , 2003, Neuron.

[26]  Rajesh Ranganathan,et al.  C. elegans Locomotory Rate Is Modulated by the Environment through a Dopaminergic Pathway and by Experience through a Serotonergic Pathway , 2000, Neuron.

[27]  J. Culotti,et al.  Dopamine counteracts octopamine signalling in a neural circuit mediating food response in C. elegans , 2009, The EMBO journal.

[28]  M. Koelle,et al.  Biogenic amine neurotransmitters in C. elegans. , 2007, WormBook : the online review of C. elegans biology.

[29]  S. W. Emmons,et al.  Patterning of dopaminergic neurotransmitter identity among Caenorhabditis elegans ray sensory neurons by a TGFbeta family signaling pathway and a Hox gene. , 1999, Development.

[30]  Gary Ruvkun,et al.  The unc-86 gene product couples cell lineage and cell identity in C. elegans , 1990, Cell.

[31]  S. R. Wicks,et al.  CHE-3, a cytosolic dynein heavy chain, is required for sensory cilia structure and function in Caenorhabditis elegans. , 2000, Developmental biology.

[32]  G. Ruvkun,et al.  Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant , 2000, Nature.

[33]  H. Horvitz,et al.  Mutations in the Caenorhabditis elegans Serotonin Reuptake Transporter MOD-5 Reveal Serotonin-Dependent and -Independent Activities of Fluoxetine , 2001, The Journal of Neuroscience.

[34]  C. Wysocki,et al.  Ability to perceive androstenone can be acquired by ostensibly anosmic people. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[35]  R. F. Thompson,et al.  Habituation: a model phenomenon for the study of neuronal substrates of behavior. , 1966, Psychological review.

[36]  Tim Tully,et al.  Dissection of memory formation: from behavioral pharmacology to molecular genetics , 1995, Trends in Neurosciences.

[37]  Cornelia I Bargmann,et al.  Reprogramming Chemotaxis Responses: Sensory Neurons Define Olfactory Preferences in C. elegans , 1997, Cell.

[38]  Cori Bargmann,et al.  A Putative Cyclic Nucleotide–Gated Channel Is Required for Sensory Development and Function in C. elegans , 1996, Neuron.

[39]  R MELZACK,et al.  The perception of pain. , 1961, Scientific American.

[40]  W. Schafer,et al.  The Insulin/PI 3-Kinase Pathway Regulates Salt Chemotaxis Learning in Caenorhabditis elegans , 2006, Neuron.

[41]  S. Rademakers,et al.  Gustatory plasticity in C. elegans involves integration of negative cues and NaCl taste mediated by serotonin, dopamine, and glutamate. , 2008, Learning & memory.

[42]  C. Rankin,et al.  Investigations of learning and memory in Caenorhabditis elegans. , 2006, International review of neurobiology.

[43]  M. Millan,et al.  The induction of pain: an integrative review , 1999, Progress in Neurobiology.

[44]  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.

[45]  A. Hart,et al.  Feeding status and serotonin rapidly and reversibly modulate a Caenorhabditis elegans chemosensory circuit. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[46]  A. V. Maricq,et al.  Neuronal Control of Locomotion in C. elegans Is Modified by a Dominant Mutation in the GLR-1 Ionotropic Glutamate Receptor , 1999, Neuron.

[47]  E. Kandel,et al.  Learning to modulate transmitter release: themes and variations in synaptic plasticity. , 1993, Annual review of neuroscience.

[48]  Jh Thomas,et al.  Regulation of a periodic motor program in C. elegans , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[49]  Aravinthan D. T. Samuel,et al.  Identification of Thermosensory and Olfactory Neuron-Specific Genes via Expression Profiling of Single Neuron Types , 2004, Current Biology.

[50]  Thomas M. Morse,et al.  The Fundamental Role of Pirouettes in Caenorhabditis elegans Chemotaxis , 1999, The Journal of Neuroscience.

[51]  Janet S. Duerr,et al.  The cat-1 Gene of Caenorhabditis elegansEncodes a Vesicular Monoamine Transporter Required for Specific Monoamine-Dependent Behaviors , 1999, The Journal of Neuroscience.

[52]  D. Weinshenker,et al.  Genetic and pharmacological analysis of neurotransmitters controlling egg laying in C. elegans , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[53]  S. Waddell,et al.  Drosophila olfactory memory: single genes to complex neural circuits , 2007, Nature Reviews Neuroscience.

[54]  P. Dalton,et al.  Gender-specific induction of enhanced sensitivity to odors , 2002, Nature Neuroscience.

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

[56]  Cornelia I Bargmann,et al.  Odorant-specific adaptation pathways generate olfactory plasticity in C. elegans , 1995, Neuron.

[57]  Subhajyoti De,et al.  Dopamine Mediates Context-Dependent Modulation of Sensory Plasticity in C. elegans , 2007, Neuron.

[58]  W. Schafer,et al.  A calcium-channel homologue required for adaptation to dopamine and serotonin in Caenorhabditis elegans , 1995, Nature.

[59]  J. Feldon,et al.  Mesolimbic dopaminergic pathways in fear conditioning , 2004, Progress in Neurobiology.

[60]  S. Brenner.  The genetics of Caenorhabditis elegans. , 1974, Genetics.

[61]  T. SHALLICE,et al.  Learning and Memory , 1970, Nature.

[62]  S. McIntire,et al.  Ethanol preference in C. elegans , 2009, Genes, brain, and behavior.

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

[64]  H. Horvitz,et al.  Coordinated Transcriptional Regulation of the unc-25Glutamic Acid Decarboxylase and the unc-47 GABA Vesicular Transporter by the Caenorhabditis elegans UNC-30 Homeodomain Protein , 1999, The Journal of Neuroscience.

[65]  V. Ambros,et al.  Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. , 1991, The EMBO journal.

[66]  Mark J Alkema,et al.  Tyramine Functions Independently of Octopamine in the Caenorhabditis elegans Nervous System , 2005, Neuron.

[67]  Cori Bargmann,et al.  Odorant-selective genes and neurons mediate olfaction in C. elegans , 1993, Cell.

[68]  C. Rankin,et al.  Analyses of habituation in Caenorhabditis elegans. , 2001, Learning & memory.

[69]  Takeshi Ishihara,et al.  Caenorhabditis elegans Integrates the Signals of Butanone and Food to Enhance Chemotaxis to Butanone , 2007, The Journal of Neuroscience.

[70]  D. M. Ferkey,et al.  The C. elegans D2-Like Dopamine Receptor DOP-3 Decreases Behavioral Sensitivity to the Olfactory Stimulus 1-Octanol , 2010, PloS one.

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

[72]  S. Hallam,et al.  The C. elegans NeuroD homolog cnd-1 functions in multiple aspects of motor neuron fate specification. , 2000, Development.

[73]  S. Fuke,et al.  Characterization of a novel D2‐like dopamine receptor with a truncated splice variant and a D1‐like dopamine receptor unique to invertebrates from Caenorhabditis elegans , 2005, Journal of neurochemistry.

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

[75]  A. V. Maricq,et al.  Dopamine and Glutamate Control Area-Restricted Search Behavior in Caenorhabditis elegans , 2004, The Journal of Neuroscience.

[76]  E. Walters,et al.  Common patterns of plasticity contributing to nociceptive sensitization in mammals and Aplysia , 1991, Trends in Neurosciences.