@article {1514631, title = {Automated cell annotation in multi-cell images using an improved CRF_ID algorithm}, journal = {$\#$co-first author; ^co-corresponding author; eLife https://doi.org/10.7554/eLife.89050.1}, year = {2023}, abstract = {Cell identification is an important yet difficult process in data analysis of biological images. Previously, we developed an automated cell identification method called CRF_ID and demonstrated its high performance in\ C. elegans\ whole-brain images (Chaudhary et al, 2021). However, because the method was optimized for whole-brain imaging, comparable performance could not be guaranteed for application in commonly used\ C. elegans\ multi-cell images that display a subpopulation of cells. Here, we present an advance CRF_ID 2.0 that expands the generalizability of the method to multi-cell imaging beyond whole-brain imaging. To illustrate the application of the advance, we show the characterization of CRF_ID 2.0 in multi-cell imaging and cell-specific gene expression analysis in\ C. elegans. This work demonstrates that high accuracy automated cell annotation in multi-cell imaging can expedite cell identification and reduce its subjectivity in\ C. elegans\ and potentially other biological images of various origins.}, url = {https://doi.org/10.7554/eLife.89050.1}, author = {* HyunJee$\#$ Lee and Jingting$\#$ Liang and Shivesh Chaudhary and Sihoon Moon and Zikai Yu and Taihong Wu and He Liu and Myung-Kyu Choi and Yun^ Zhang and Hang^ Lu} } @journal {1468831, title = {Pathogenic bacteria modulate pheromone response to promote mating}, volume = {613}, year = {2023}, pages = {324-331}, abstract = {

Pathogens generate ubiquitous selective pressures and host{\textendash}pathogen interactions alter social behaviours in many animals1{\textendash}4. However, very little is known about the neuronal mechanisms underlying pathogen-induced changes in social behaviour. Here we show that in adult Caenorhabditis elegans hermaphrodites, exposure to a bacterial pathogen (Pseudomonas aeruginosa) modulates sensory responses to pheromones by inducing the expression of the chemoreceptor STR-44 to promote mating. Under standard conditions, C. elegans hermaphrodites avoid a mixture of ascaroside pheromones to facilitate dispersal5{\textendash}13. We find that exposure to the pathogenic Pseudomonas bacteria enables pheromone responses in AWA sensory neurons, which mediate attractive chemotaxis, to suppress the avoidance. Pathogen exposure induces str-44 expression in AWA neurons, a process regulated by a transcription factor zip-5 that also displays a pathogen-induced increase in expression in AWA. STR-44 acts as a pheromone receptor and its function in AWA neurons is required for pathogen-induced AWA pheromone response and suppression of pheromone avoidance. Furthermore, we show that C. elegans hermaphrodites, which reproduce mainly through self-fertilization, increase the rate of mating with males after pathogen exposure and that this increase requires str-44 in AWA neurons. Thus, our results uncover a causal mechanism for pathogen-induced social behaviour plasticity, which can promote genetic diversity and facilitate adaptation of the host animals.

\ 

\ 

  • DOI:\ 10.1038/s41586-022-05561-9

\ 

}, url = {https://pubmed.ncbi.nlm.nih.gov/36599989/}, author = {* Taihong$\#$ Wu and Minghai$\#$ Ge and Min Wu and Fengyun Duan and Jingting Liang and Maoting Chen and Xicotencatl Gracida and He Liu and Wenxing Yang and Abdul Rouf Dar and Chengyin Li and Rebecca A. Butcher and Arneet L. Saltzman and Yun Zhang} } @article {1429186, title = {Forgetting generates a novel state that is reactivatable}, journal = {$\#$: co-first author. Science Advances}, volume = {8}, year = {2022}, pages = {eabi9071}, abstract = {

Forgetting is defined as a time-dependent decline of a memory. However, it is not clear whether forgetting reverses the learning process to return the brain to the naive state. Here, using the aversive olfactory learning of pathogenic bacteria in\ C. elegans, we show that forgetting generates a novel state of the nervous system that is distinct from the naive state or the learned state. A transient exposure to the training condition or training odorants reactivates this novel state to elicit the previously learned behavior. An AMPA receptor and a type II serotonin receptor act in the central neuron of the learning circuit to decrease and increase the speed to reach this novel state, respectively. Together, our study systematically characterizes forgetting and uncovers conserved mechanisms underlying the rate of forgetting.\ 

  • PMID:\ 35148188
  • DOI:\ 10.1126/sciadv.abi9071
}, url = {https://pubmed.ncbi.nlm.nih.gov/35148188/}, author = {* Liu, H$\#$ and Wu, T$\#$ and Canales, XG and Wu, M. and Choi, MK and Duan, F and Calarco, J. A. and Zhang, Y.} } @article {1429190, title = {Redundant neural circuits regulate olfactory integration}, journal = {PLoS Genetics}, volume = {18}, year = {2022}, pages = {e1010029}, abstract = {

Olfactory integration is important for survival in a natural habitat. However, how the nervous system processes signals of two odorants present simultaneously to generate a coherent behavioral response is poorly understood. Here, we characterize circuit basis for a form of olfactory integration in Caenorhabditis elegans. We find that the presence of a repulsive odorant, 2-nonanone, that signals threat strongly blocks the attraction of other odorants, such as isoamyl alcohol (IAA) or benzaldehyde, that signal food. Using a forward genetic screen, we found that genes known to regulate the structure and function of sensory neurons, osm-5 and osm-1, played a critical role in the integration process. Loss of these genes mildly reduces the response to the repellent 2-nonanone and disrupts the integration effect. Restoring the function of OSM-5 in either AWB or ASH, two sensory neurons known to mediate 2-nonanone-evoked avoidance, is sufficient to rescue. Sensory neurons AWB and downstream interneurons AVA, AIB, RIM that play critical roles in olfactory sensorimotor response are able to process signals generated by 2-nonanone or IAA or the mixture of the two odorants and contribute to the integration. Thus, our results identify redundant neural circuits that regulate the robust effect of a repulsive odorant to block responses to attractive odorants and uncover the neuronal and cellular basis for this complex olfactory task.

  • PMID:\ 35100258
  • \ 
  • PMCID:\ PMC8830790
  • \ 
  • DOI:\ 10.1371/journal.pgen.1010029

\ 

}, url = {https://pubmed.ncbi.nlm.nih.gov/35100258/}, author = {* Yang, W and Wu, T. and Tu, S and Qin, Y. and Shen, C and J. Li and Choi, MK and Duan, F and Zhang, Y.} } @article {1413366, title = {Neuronal control of maternal provisioning in response to social cues}, journal = {^co-corresponding author; Science Advances}, volume = {7}, year = {2021}, pages = {8782}, abstract = {

Mothers contribute cytoplasmic components to their progeny in a process called maternal provisioning. Provisioning is influenced by the parental environment, but the molecular pathways that transmit environmental cues between generations are not well understood. Here, we show that, in\ Caenorhabditis elegans, social cues modulate maternal provisioning to regulate gene silencing in offspring. Intergenerational signal transmission depends on a pheromone-sensing neuron and neuronal FMRFamide (Phe-Met-Arg-Phe){\textendash}like peptides. Parental FMRFamide-like peptide signaling dampens oxidative stress resistance and promotes the deposition of mRNAs for translational components in progeny, which, in turn, reduces gene silencing. This study identifies a previously unknown pathway for intergenerational communication that links neuronal responses to maternal provisioning. We suggest that loss of social cues in the parental environment represents an adverse environment that stimulates stress responses across generations.

DOI: 10.1126/sciadv.abf8782

}, url = {https://advances.sciencemag.org/content/7/34/eabf8782}, author = {* Wasson, Jadiel A. and Gareth Harris and Keppler-Ross, Sabine and Brock, Trisha J. and Dar, Abdul R. and Butcher, Rebecca A. and Sylvia E. J. Fische and Kagias, Konstantinos and Clardy, Jon and Yun^ Zhang and Susan E.^ Mango} } @article {1412341, title = {Deorphanization of novel biogenic amine-gated ion channels identifies a new serotonin receptor for learning}, journal = {Current Biology}, volume = {2021}, year = {2021}, pages = {036}, abstract = {

Pentameric ligand-gated ion channels (LGICs) play conserved, critical roles in both excitatory and inhibitory synaptic transmission and can be activated by diverse neurochemical ligands. We have performed a characterization of orphan channels from the nematode C. elegans, identifying five new monoamine-gated LGICs with diverse functional properties and expression postsynaptic to aminergic neurons. These include polymodal anion channels activated by both dopamine and tyramine, which may mediate inhibitory transmission by both molecules in vivo. Intriguingly, we also find that a novel serotonin-gated cation channel, LGC-50, is essential for aversive olfactory learning of pathogenic bacteria, a process known to depend on serotonergic neurotransmission. Remarkably, the redistribution of LGC-50 to neuronal processes is modulated by olfactory conditioning, and lgc-50 point mutations that cause misregulation of receptor membrane expression interfere with olfactory learning. Thus, the intracellular trafficking and localization of these receptors at synapses may represent a molecular cornerstone of the learning mechanism.

\ 

DOI:\ 10.1016/j.cub.2021.07.036

}, url = {https://pubmed.ncbi.nlm.nih.gov/34388373/$\#$affiliation-1}, author = {Morud, Julia and Hardege, Iris and He Liu and Taihong Wu and Myung-Kyu Choi and Basu, Swaraj and Yun Zhang and Schafer, William R} } @article {1398125, title = {Redundant neural circuits regulate olfactory masking}, journal = {bioRxiv}, volume = {2021}, year = {2021}, pages = {440489}, abstract = {

Olfactory masking is a complex olfactory response found in humans. However, the mechanisms whereby the presence of one odorant masks the sensory and behavioral responses elicited by another odorant are poorly understood. Here, we report that Caenorhabditis elegans displays olfactory masking and that the presence of a repulsive odorant, 2-nonanone, that signals threat strongly masks the attraction of other odorants, such as isoamyl alcohol (IAA) or benzaldehyde that signals food. Using a forward genetic screen, we found that several genes, osm-5, osm-1, and dyf-7, known to regulate the structure and function of sensory neurons played a critical role in olfactory masking. Loss of these genes mildly reduces the response to 2-nonanone and disrupts the masking effect of 2-nonanone. Restoring the function of OSM-5 in either AWB or ASH, two sensory neurons known to mediate 2-nonanone-evoked avoidance, is sufficient to rescue olfactory masking. AWB is activated by the removal of 2-nonanone stimulation or the onset of IAA; however, the mixture of 2-nonanone and IAA stimulates AWB similarly as 2-nonanone alone, masking the cellular effect of IAA. The latency of the AWB response is critical for the masking effect. Thus, our results identify redundant neural circuits that regulate the robust masking effect of a repulsive odorant and uncover the neuronal and cellular basis for this complex olfactory task.

doi:\ https://doi.org/10.1101/2021.04.19.440489

}, url = {https://www.biorxiv.org/content/10.1101/2021.04.19.440489v1}, author = {*Yang, W. and Wu, T. and Tu, S and Choi, M-K and Duan, F and Zhang, Y.} } @article {1392553, title = {Neuronal control of maternal provisioning in response to social cues}, journal = {$\#$: co-first author; ^: co-corresponding author. bioRxiv}, volume = {10.1101}, year = {2021}, pages = {429208}, abstract = {

Mothers contribute cytoplasmic components to their progeny in a process called maternal provisioning. Provisioning is influenced by the parental environment, but the molecular pathways that transmit environmental cues from mother to progeny are not well understood. Here we show that in\ C. elegans, social cues modulate maternal provisioning to regulate gene silencing in offspring. Intergenerational signal transmission depends on a pheromone-sensing neuron and neuronal FMRF (Phe-Met-Arg-Phe)-like peptides. Parental FMRF signaling promotes the deposition of mRNAs for translational components in progeny, which in turn reduces gene silencing. Previous studies had implicated FMRF signaling in short-term responses such as modulated feeding behavior in response to the metabolic state1,2, but our data reveal a broader role, to coordinate energetically expensive processes such as translation and maternal provisioning. This study identifies a new pathway for intergenerational communication, distinct from previously discovered pathways involving small RNAs and chromatin, that links sensory perception to maternal provisioning.

\ 

\ 

doi:\ https://doi.org/10.1101/2021.02.01.429208

}, url = {https://www.biorxiv.org/content/10.1101/2021.02.01.429208v1}, author = {* Wasson, Jadiel A. $\#$ and Harris, Gareth $\#$ and Keppler-Ross, Sabine and Brock, Trisha J. and Dar, Abdul R. and Butcher, Rebecca A. and Fischer, Sylvia E.J. and Kagias, Konstantinos and Clardy, Jon and Zhang, Yun^ and Mango, Susan^} } @article {1392550, title = {Nature{\textquoteright}s gift to neuroscience}, journal = {J Neurogenet}, volume = {34}, year = {2020}, pages = {223-224}, abstract = {

PMID:\ 33446019

DOI:\ 10.1080/01677063.2020.1841760

}, url = {https://www.tandfonline.com/doi/full/10.1080/01677063.2020.1841760}, author = {Alcedo, Joy and Jin, Yishi and Portman, Douglas S and Prahlad, Veena and Raizen, David and Rapti, Georgia and Xu, X Z Shawn and Yun Zhang and Wu, Chun-Fang} } @article {1379756, title = {What can a worm learn in a bacteria-rich habitat?}, journal = {J Neurogenet .}, year = {2020}, pages = {1-9}, abstract = {

With a nervous system that has only a few hundred neurons,\ Caenorhabditis elegans\ was initially not regarded as a model for studies on learning. However, the collective effort of the\ C. elegans\ field in the past several decades has shown that the worm displays plasticity in its behavioral response to a wide range of sensory cues in the environment. As a bacteria-feeding worm,\ C. elegans\ is highly adaptive to the bacteria enriched in its habitat, especially those that are pathogenic and pose a threat to survival. It uses several common forms of behavioral plasticity that last for different amounts of time, including imprinting and adult-stage associative learning, to modulate its interactions with pathogenic bacteria. Probing the molecular, cellular and circuit mechanisms underlying these forms of experience-dependent plasticity has identified signaling pathways and regulatory insights that are conserved in more complex animals.

PMID:\ 33054485

\ 

\ 

\ 

\ 

\ 

\ 

\  DOI:\ 10.1080/01677063.2020.1829614

}, url = {https://pubmed.ncbi.nlm.nih.gov/33054485/}, author = {*Liu, H and Zhang, Y.} } @article {1379650, title = {Global regulatory features of alternative splicing across tissues and within the nervous system of C. elegans}, journal = {Genome Research}, year = {2020}, pages = {120}, abstract = {

Alternative splicing plays a major role in shaping tissue-specific transcriptomes. Among the broad tissue types present in metazoans, the central nervous system contains some of the highest levels of alternative splicing. While many documented examples of splicing differences between broad tissue-types exist, there remains much to be understood about the splicing factors and the\ cis\ sequence elements controlling tissue and neuron subtype-specific splicing patterns. Using Translating Ribosome Affinity Purification coupled with deep-sequencing (TRAP-seq) in\ C. elegans, we have obtained high coverage profiles of ribosome-associated mRNA for three broad tissue classes (nervous system, muscle, and intestine) and two neuronal subtypes (dopaminergic and serotonergic neurons). We have identified hundreds of splice junctions that exhibit distinct splicing patterns between tissue types or within the nervous system. Alternative splicing events differentially regulated between tissues are more often frame-preserving, conserved across\ Caenorhabditis\ species and enriched in specific\ cis\ regulatory motifs. Utilizing this information, we have identified a likely mechanism of splicing repression by the RNA-binding protein UNC-75/CELF via interactions with\ cis\ elements that overlap a 5{\textquoteright} splice site. Alternatively spliced exons also overlap more frequently with intrinsically disordered peptide regions than constitutive exons. Moreover, regulated exons are often shorter than constitutive exons but are flanked by longer intron sequences. Among these tissue-regulated exons are several highly conserved microexons less than 27 nucleotides in length. Collectively, our results indicate a rich layer of tissue-specific gene regulation at the level of alternative splicing in\ C. elegans\ that parallel the evolutionary forces and constraints observed across metazoa.

\ 

\ 

\ 

\ 

PMID:\ 33127752 DOI:\ 10.1101/gr.267328.120

}, url = {https://pubmed.ncbi.nlm.nih.gov/33127752/$\#$affiliation-4}, author = {Koterniak, Bina and Pilaka, Pallavi P and Gracida, Xicotencatl and Schneider, Lisa-Marie and Priti{\v s}anac, Iva and Yun Zhang and Calarco, John A} } @article {1377176, title = {C. elegans aversive olfactory learning generates diverse intergenerational effects.}, journal = {J Neurogenet}, volume = {10}, year = {2020}, pages = {1-11}, abstract = {

Parental experience can modulate the behavior of their progeny. While the molecular mechanisms underlying parental effects or inheritance of behavioral traits have been studied under several environmental conditions, it remains largely unexplored how the nature of parental experience affects the information transferred to the next generation. To address this question, we used\ C. elegans, a nematode that feeds on bacteria in its habitat. Some of these bacteria are pathogenic and the worm learns to avoid them after a brief exposure. We found, unexpectedly, that a short parental experience increased the preference for the pathogen in the progeny. Furthermore, increasing the duration of parental exposure switched the response of the progeny from attraction to avoidance. To characterize the underlying molecular mechanisms, we found that the RNA-dependent RNA Polymerase (RdRP) RRF-3, required for the biogenesis of 26 G endo-siRNAs, regulated both types of intergenerational effects. Together, we show that different parental experiences with the same environmental stimulus generate different effects on the behavior of the progeny through small RNA-mediated regulation of gene expression.

\ 

doi: 10.1080/01677063.2020.1819265
}, url = {https://pubmed.ncbi.nlm.nih.gov/32940103/}, author = {* Pereira, Ana Goncalves and Gracida, Xicotencatl and Kagias, Konstantinos and Yun Zhang} } @article {1377174, title = {Deorphanisation of novel biogenic amine-gated ion channels identifies a new serotonin receptor for learning}, journal = {bioRxiv }, volume = {10}, year = {2020}, abstract = {

Pentameric ligand-gated ion channels (LGCs) play conserved, critical roles in fast synaptic transmission, and changes in LGC expression and localisation are thought to underlie many forms of learning and memory. The\ C. elegans\ genome encodes a large number of LGCs without a known ligand or function. Here, we deorphanize five members of a family of Cys-loop LGCs by characterizing their diverse functional properties that are activated by biogenic amine neurotransmitters. To analyse the neuronal function of these LGCs, we show that a novel serotonin-gated cation channel, LGC-50, is essential for aversive olfactory learning.\ lgc-50\ mutants show a specific defect in learned olfactory avoidance of pathogenic bacteria, a process known to depend on serotonergic neurotransmission. Remarkably, the expression of LGC-50 in neuronal processes is enhanced by olfactory conditioning; thus, the regulated expression of these receptors at synapses appears to represent a molecular cornerstone of the learning mechanism.

doi:\ https://doi.org/10.1101/2020.09.17.301382}, url = {https://www.biorxiv.org/content/10.1101/2020.09.17.301382v1}, author = {Morud, Julia and Hardege, Iris and He Liu and Taihong Wu and Basu, Swaraj and Yun Zhang and Schafer, William R} } @article {1354821, title = {NMDAR-mediated modulation of gap junction circuit regulates olfactory learning in C. elegans}, journal = {Nature Communications }, volume = {11}, year = {2020}, abstract = {

Modulation of gap junction-mediated electrical synapses is a common form of neural plasticity. However, the behavioral consequence of the modulation and the underlying molecular cellular mechanisms are not understood. Here, using a\ C. elegans\ circuit of interneurons that are connected by gap junctions, we show that modulation of the gap junctions facilitates olfactory learning. Learning experience weakens the gap junctions and induces a repulsive sensory response to the training odorants, which together decouple the responses of the interneurons to the training odorants to generate learned olfactory behavior. The weakening of the gap junctions results from downregulation of the abundance of a gap junction molecule, which is regulated by cell-autonomous function of the worm homologs of a NMDAR subunit and CaMKII. Thus, our findings identify the function of a gap junction modulation in an in vivo model of learning and a conserved regulatory pathway underlying the modulation.

}, url = {https://www.nature.com/articles/s41467-020-17218-0}, author = {*Choi, Myung-Kyu, and Liu, H and Taihong Wu and Wenxing Yang and Yun Zhang} } @article {1225987, title = {Pheromones modulate learning by regulating the balanced signals of two insulin-like peptides.}, journal = {Neuron}, volume = {2019.09.006}, year = {2019}, month = {October 29, 2019}, abstract = {

Social environment modulates learning through unknown mechanisms. Here, we report that a pheromone mixture that signals overcrowding inhibits\ C.\ elegans\ from learning to avoid pathogenic bacteria. We find that learning depends on the balanced signaling of two insulin-like peptides (ILPs), INS-16 and INS-4, which act respectively in the pheromone-sensing neuron ADL and the bacteria-sensing neuron AWA. Pheromone exposure inhibits learning by disrupting this balance: it activates ADL and increases expression of\ ins-16, and this cellular effect reduces AWA activity and AWA-expressed\ ins-4. The activities of the sensory neurons are required for learning and the expression of the ILPs. Interestingly, pheromones also promote the ingestion of pathogenic bacteria while increasing resistance to the pathogen. Thus, the balance of the ILP signals integrates social information into the learning process as part of a coordinated adaptive response that allows consumption of harmful food during times of high population density.

DOI:https://doi.org/10.1016/j.neuron.2019.09.006

\ 

}, url = {https://www.cell.com/neuron/fulltext/S0896-6273(19)30779-2$\#$\%20}, author = {* Wu, T. and Duan, F. and Yang, W. and Liu, H. and Caballero, A. and Fernandes de Abreu, D. A. and Dar, A.R. and Alcedo, J. and Ch{\textquoteright}ng, Q. and Butcher, R.A. and Zhang, Y.} } @article {1225986, title = {Learning of pathogenic bacteria in adult C. elegans bidirectionally regulates pathogen response in the progeny.}, journal = {BioRxiv}, volume = {doi:10.1101/500264}, year = {2019}, abstract = {

Parental experience can generate adaptive changes in the behavioral and physiological traits of the offspring1{\textendash}3. However, the biological properties of this intergenerational regulation and the underlying molecular and cellular mechanism are not well understood. Here, we show that the experience of learning to avoid pathogenic bacteria in\ C. elegans\ alters the behavioral response to the pathogen in the progeny through the endogenous RNA interference (RNAi) pathway. We previously show that the adult\ C. elegans\ learns to avoid the smell of pathogenic bacteria, such as the\ Pseudomonas aeruginosa\ strain PA14, after feeding on the pathogen for a few hours4,5. Here, we report that this learning experience can bidirectionally regulate the olfactory response to PA14 in the progeny that are never directly exposed to the pathogen. The olfactory preference for PA14 in these progeny is linearly correlated with the learned avoidance of PA14 in their mothers. If the mothers show strong learning of PA14, their progeny avoid PA14; intriguingly, if the mothers show weak learning of PA14, the progeny prefer PA14, suggesting that the PA14-trained mothers transmit both the negative and positive information of PA14 to their progeny. The intergenerational behavioral effect results from an altered behavioral decision regulated by an olfactory sensorimotor neural circuit. Learning to avoid the pathogen also influences the development of the progeny, which is regulated independently from the behavioral change. Animals mutated for the RRF-3/RNA-directed RNA polymerase, a master regulator for the synthesis of the small interfering RNAs that are maternally inherited or in the soma6,7, display the normal naive and learned response to PA14 but are defective in regulating the olfactory response to PA14 in their progeny. Our results characterize an intergenerational effect that allows the progeny to rapidly adapt to an environmental condition that is critical for survival.

doi:\ https://doi.org/10.1101/500264}, url = {https://www.biorxiv.org/content/10.1101/500264v2}, author = {* Pereira, A. and Gracida, X. and Kagias, K. and Zhang, Y.} } @article {1225984, title = {Molecular and cellular modulators for multisensory integration in C. elegans}, journal = {PLoS Genetics}, volume = {15(3): e1007706}, year = {2019}, abstract = {

In the natural environment, animals often encounter multiple sensory cues that are simultaneously present. The nervous system integrates the relevant sensory information to generate behavioral responses that have adaptive values. However, the neuronal basis and the modulators that regulate integrated behavioral response to multiple sensory cues are not well defined. Here, we address this question using a behavioral decision in C. elegans when the animal is presented with an attractive food source together with a repulsive odorant. We identify specific sensory neurons, interneurons and neuromodulators that orchestrate the decision-making process, suggesting that various states and contexts may modulate the multisensory integration. Among these modulators, we characterize a new function of a conserved TGF-β pathway that regulates the integrated decision by inhibiting the signaling from a set of central neurons. Interestingly, we find that a common set of modulators, including the TGF-β pathway, regulate the integrated response to the pairing of different foods and repellents. Together, our results provide mechanistic insights into the modulatory signals regulating multisensory integration.

https://doi.org/10.1371/journal.pgen.1007706

}, url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007706}, author = {* Harris, G. and Wu, T. and Linfield, G. and Choi, M-K. and Liu, H. and Zhang, Y.} } @article {1225985, title = {Neuronal sub-compartmentalization: a strategy to optimize neuronal function. $\#$: Co-first authors. \&:Co-senior authors.}, journal = {Biol Rev Camb Philos Soc.}, volume = {doi:10.1111/brv.12487}, year = {2018}, abstract = {Neurons are highly polarized cells that consist of three main structural and functional domains: a cell body or soma, an axon, and dendrites. These domains contain smaller compartments with essential roles for proper neuronal function, such as the axonal presynaptic boutons and the dendritic postsynaptic spines. The structure and function of these compartments have now been characterized in great detail. Intriguingly, however, in the last decade additional levels of compartmentalization within the axon and the dendrites have been identified, revealing that these structures are much more complex than previously thought. Herein we examine several types of structural and functional sub-compartmentalization found in neurons of both vertebrates and invertebrates. For example, in mammalian neurons the axonal initial segment functions as a sub-compartment to initiate the action potential, to select molecules passing into the axon, and to maintain neuronal polarization. Moreover, work in Drosophila melanogaster has shown that two distinct axonal guidance receptors are precisely clustered in adjacent segments of the commissural axons both in vivo and in vitro, suggesting a cell-intrinsic mechanism underlying the compartmentalized receptor localization. In Caenorhabditis elegans, a subset of interneurons exhibits calcium dynamics that are localized to specific sections of the axon and control the gait of navigation, demonstrating a regulatory role of compartmentalized neuronal activity in behaviour. These findings have led to a number of new questions, which are important for our understanding of neuronal development and function. How are these sub-compartments established and maintained? What molecular machinery and cellular events are involved? What is their functional significance for the neuron? Here, we reflect on these and other key questions that remain to be addressed in this expanding field of biology.}, url = {https://onlinelibrary.wiley.com/doi/full/10.1111/brv.12487}, author = {*Donato, A. and Kagias, K. and Zhang, Y.$\#$ and Hilliard, M.A.\&} } @article {1225983, title = {Thioredoxin shapes C. elegans sensory response to Pseudomonas produced nitric oxide. $\#$: Co-first authors. \&: Co-senior authors.}, journal = {eLife}, volume = {pii: e36833}, year = {2018}, abstract = {

Nitric oxide (NO) is released into the air by NO-producing organisms; however, it is unclear if animals utilize NO as a sensory cue. We show that C. elegans avoids Pseudomonas aeruginosa (PA14) in part by detecting PA14-produced NO. PA14 mutants deficient for NO production fail to elicit avoidance and NO donors repel worms. PA14 and NO avoidance are mediated by a chemosensory neuron (ASJ) and these responses require receptor guanylate cyclases and cyclic nucleotide gated ion channels. ASJ exhibits calcium increases at both the onset and removal of NO. These NO-evoked ON and OFF calcium transients are affected by a redox sensing protein, TRX-1/thioredoxin. TRX-1{\textquoteright}s trans-nitrosylation activity inhibits the ON transient whereas TRX-1{\textquoteright}s de-nitrosylation activity promotes the OFF transient. Thus, C. elegans exploits bacterially produced NO as a cue to mediate avoidance and TRX-1 endows ASJ with a bi-phasic response to NO exposure.

https://doi.org/10.7554/eLife.36833.001
}, url = {https://elifesciences.org/articles/36833}, author = {* Hao, Y.$\#$ and Yang, W.$\#$ and Hall, Q. and Ren, J. and Zhang, Y.\& and Kaplan, J.M.\&} } @article {1225982, title = {Cholinergic sensorimotor integration regulates olfactory steering}, journal = {Neuron}, volume = {97}, year = {2018}, pages = {390-405}, abstract = {Sensorimotor integration regulates goal-directedmovements. We study the signaling mechanismsunderlying sensorimotor integration inC.elegansduring olfactory steering, when the sinusoidal move-ments of the worm generate an in-phase oscillation inthe concentration of the sampled odorant. We showthat cholinergic neurotransmission encodes theoscillatory sensory response and the motor state ofhead undulations by acting through an acetylcho-line-gated channel and a muscarinic acetylcholinereceptor, respectively. These signals convergeon two axonal domains of an interneuron RIA,where the sensory-evoked signal suppresses themotor-encoding signal to transform the spatial infor-mation of the odorant into the asymmetry betweenthe axonal activities. The asymmetric synaptic out-puts of the RIA axonal domains generate a direc-tional bias in the locomotory trajectory. Experiencealters the sensorimotor integration to generatespecific behavioral changes. Our study reveals howcholinergic neurotransmission, which can representsensory and motor information in the mammalianbrain, regulates sensorimotor integration duringgoal-directed locomotions.}, url = {https://www.cell.com/action/showPdf?pii=S0896-6273\%2817\%2931126-1}, author = {* Liu, H. and Yang, W. and Wu, T. and Duan, F and Soucy, E. and Jin, X. and Zhang, Y.} } @article {1096566, title = {An Elongin-Cullin-SOCS-box Complex Regulates Stress-induced Serotonergic Neuromodulation. \&: Co-senior authors.}, journal = {Cell Reports}, volume = {10.1016}, year = {2017}, pages = {042}, abstract = {

Summary

Neuromodulatory cells transduce environmental information into long-lasting behavioral responses. However, the mechanisms governing how neuronal cells influence behavioral plasticity are difficult to\ characterize. Here, we adapted the translating ribosome affinity purification (TRAP) approach in C.\ elegans to profile ribosome-associated mRNAs from three major tissues and the neuromodulatory dopaminergic and serotonergic cells. We identified elc-2, an Elongin C ortholog, specifically expressed in stress-sensing amphid neuron dual ciliated sensory ending (ADF) serotonergic sensory neurons, and we found that it plays a role in mediating a long-lasting change in serotonin-dependent feeding behavior induced by heat stress. We demonstrate that ELC-2 and the von Hippel-Lindau protein VHL-1, components of an Elongin-Cullin-SOCS box (ECS) E3 ubiquitin ligase, modulate this behavior after experiencing stress. Also, heat stress induces a transient redistribution of ELC-2, becoming more nuclearly enriched. Together, our results demonstrate dynamic regulation of an E3 ligase and a role for an ECS complex in neuromodulation and control of lasting behavioral states.

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DOI: 10.1016/j.celrep.2017.11.042
}, url = {http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31679-0}, author = {*Gracida, X and Harris, G. and Zhang, Y.\& and Calarco, J.A\&} } @article {1000821, title = {An Aversive Response to Osmotic Upshift in \<i\>Caenorhabditis elegans\</i\>. }, journal = {eNeuro}, volume = {4}, year = {2017}, pages = {pii: ENEURO.0282-16.2017}, abstract = {

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Environmental osmolarity presents a common type of sensory stimulus to animals. While behavioral responses to osmotic changes are important for maintaining a stable intracellular osmolarity, the underlying mechanisms are not fully understood. In the natural habitat of Caenorhabditis elegans, changes in environmental osmolarity are commonplace. It is known that the nematode acutely avoids shocks of extremely high osmolarity. Here, we show that C. elegans also generates gradually increased aversion of mild upshifts in environmental osmolarity. Different from an acute avoidance of osmotic shocks that depends on the function of a transient receptor potential vanilloid channel, the slow aversion to osmotic upshifts requires the cGMP-gated sensory channel subunit TAX-2. TAX-2 acts in several sensory neurons that are exposed to body fluid to generate the aversive response through a motor network that underlies navigation. Osmotic upshifts activate the body cavity sensory neuron URX, which is known to induce aversion upon activation. Together, our results characterize the molecular and cellular mechanisms underlying a novel sensorimotor response to osmotic stimuli and reveal that C. elegans engages different behaviors and the underlying mechanisms to regulate responses to extracellular osmolarity.

eNeuro. 2017 Apr 21;4(2).\ 

doi: 10.1523/ENEURO.0282-16.2017.\ 

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}, author = {*Yu, J and Yang, W. and Liu, H and Y Hao and Zhang, Y.} } @article {1000816, title = {Multisensory integration in C. elegans.}, journal = {Curr Opin Neurobiol}, volume = {43}, year = {2017}, pages = {110-118}, abstract = {

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Multisensory integration is a neural process by which signals from two or more distinct sensory channels are simultaneously processed to form a more coherent representation of the environment. Multisensory integration, especially when combined with a survey of internal states, provides selective advantages for animals navigating complex environments. Despite appreciation of the importance of multisensory integration in behavior, the underlying molecular and cellular mechanisms remain poorly understood. Recent work looking at how Caenorhabditis elegans makes multisensory decisions has yielded mechanistic insights into how a relatively simple and well-defined nervous system employs circuit motifs of defined features, synaptic signals and extrasynaptic neurotransmission, as well as neuromodulators in processing and integrating multiple sensory inputs to generate flexible and adaptive behavioral outputs.

PMID:\ 28273525

DOI: https://doi.org/10.1016/j.conb.2017.01.005\ 

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}, author = {*Ghosh, DD and Nitabach, MN and Zhang, Y. and Harris, G.} } @article {821406, title = {An extrasynaptic GABAergic signal modulates a pattern of forward movement in Caenorhabditis elegans. $\#$: Co-first authors.}, journal = {eLife}, volume = {5}, year = {2016}, month = {3 May}, abstract = {

As a common neurotransmitter in the nervous system, γ-aminobutyric acid (GABA) modulates locomotory patterns in both vertebrates and invertebrates. However, the signaling mechanisms underlying the behavioral effects of GABAergic modulation are not completely understood. Here, we demonstrate that a GABAergic signal in C. elegans modulates the amplitude of undulatory head bending through extrasynaptic neurotransmission and conserved metabotropic receptors. We show that the GABAergic RME head motor neurons generate undulatory activity patterns that correlate with head bending and the activity of RME causally links with head bending amplitude. The undulatory activity of RME is regulated by a pair of cholinergic head motor neurons SMD, which facilitate head bending, and inhibits SMD to limit head bending. The extrasynaptic neurotransmission between SMD and RME provides a gain control system to set head bending amplitude to a value correlated with optimal efficiency of forward movement.

DOI: http://dx.doi.org/10.7554/eLife.14197.001

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}, author = {* Shen, Y.$\#$ and Wen, Q.$\#$ and Liu, H.$\#$ and Zhong, C and Qin, Y. and Harris, G. and Kawano, T and Wu, M. and Xu, T and Samuel, A and Zhang, Y.} } @article {528666, title = {Bidirectional thermotaxis in Caenorhabditis elegans is mediated by distinct sensorimotor strategies driven by the AFD thermosensory neurons}, journal = {^co-corresponding author; Proc Natl Acad Sci U S A}, volume = {111}, number = {7}, year = {2014}, note = {

Luo, LinjiaoCook, NathanVenkatachalam, VivekMartinez-Velazquez, Luis AZhang, XiaodongCalvo, Ana CHawk, JoshMacInnis, Bronwyn LFrank, MichelleNg, Jia Hong RayKlein, MasonGershow, MarcHammarlund, MarcGoodman, Miriam BColon-Ramos, Daniel AZhang, YunSamuel, Aravinthan D Teng1P01GM103770/GM/NIGMS NIH HHS/8DP1GM105383-05/DP/NCCDPHP CDC HHS/P01 GM103770/GM/NIGMS NIH HHS/R01 DC009852/DC/NIDCD NIH HHS/R01 NS076558/NS/NINDS NIH HHS/R01NS076558/NS/NINDS NIH HHS/R21 NS061147/NS/NINDS NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2014/02/20 06:00Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2776-81. doi: 10.1073/pnas.1315205111. Epub 2014 Feb 3.

}, month = {Feb 18}, pages = {2776-81}, abstract = {

The nematode Caenorhabditis elegans navigates toward a preferred temperature setpoint (Ts) determined by long-term temperature exposure. During thermotaxis, the worm migrates down temperature gradients at temperatures above Ts (negative thermotaxis) and performs isothermal tracking near Ts. Under some conditions, the worm migrates up temperature gradients below Ts (positive thermotaxis). Here, we analyze positive and negative thermotaxis toward Ts to study the role of specific neurons that have been proposed to be involved in thermotaxis using genetic ablation, behavioral tracking, and calcium imaging. We find differences in the strategies for positive and negative thermotaxis. Negative thermotaxis is achieved through biasing the frequency of reorientation maneuvers (turns and reversal turns) and biasing the direction of reorientation maneuvers toward colder temperatures. Positive thermotaxis, in contrast, biases only the direction of reorientation maneuvers toward warmer temperatures. We find that the AFD thermosensory neuron drives both positive and negative thermotaxis. The AIY interneuron, which is postsynaptic to AFD, may mediate the switch from negative to positive thermotaxis below Ts. We propose that multiple thermotactic behaviors, each defined by a distinct set of sensorimotor transformations, emanate from the AFD thermosensory neurons. AFD learns and stores the memory of preferred temperatures, detects temperature gradients, and drives the appropriate thermotactic behavior in each temperature regime by the flexible use of downstream circuits.

}, keywords = {*Models, Neurological, Animals, Caenorhabditis elegans/*physiology, Memory, Long-Term/*physiology, Movement/*physiology, Neurons/*physiology, Temperature, Thermosensing/*physiology}, isbn = {1091-6490 (Electronic)0027-8424 (Linking)}, author = {* Luo, L.^ and Cook, N. and Venkatachalam, V. and Martinez-Velazquez, L. A. and Zhang, X. and Calvo, A. C. and Hawk, J. and MacInnis, B. L. and Frank, M. and Ng, J. H. and Klein, M. and Gershow, M. and Hammarlund, M. and Goodman, M. B.^ and Colon-Ramos, D. A.^ and Zhang, Y.^ and Samuel, A. D.^} } @article {528671, title = {Dissecting the signaling mechanisms underlying recognition and preference of food odors}, journal = {J Neurosci}, volume = {34}, number = {28}, year = {2014}, note = {

Harris, GarethShen, YuHa, HeonickDonato, AlessandraWallis, SamuelZhang, XiaodongZhang, YunengP40 00010440/PHS HHS/R01 DC009852/DC/NIDCD NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}t2014/07/11 06:00J Neurosci. 2014 Jul 9;34(28):9389-403. doi: 10.1523/JNEUROSCI.0012-14.2014.

}, month = {Jul 9}, pages = {9389-403}, abstract = {

Food is critical for survival. Many animals, including the nematode Caenorhabditis elegans, use sensorimotor systems to detect and locate preferred food sources. However, the signaling mechanisms underlying food-choice behaviors are poorly understood. Here, we characterize the molecular signaling that regulates recognition and preference between different food odors in C. elegans. We show that the major olfactory sensory neurons, AWB and AWC, play essential roles in this behavior. A canonical Galpha-protein, together with guanylate cyclases and cGMP-gated channels, is needed for the recognition of food odors. The food-odor-evoked signal is transmitted via glutamatergic neurotransmission from AWC and through AMPA and kainate-like glutamate receptor subunits. In contrast, peptidergic signaling is required to generate preference between different food odors while being dispensable for the recognition of the odors. We show that this regulation is achieved by the neuropeptide NLP-9 produced in AWB, which acts with its putative receptor NPR-18, and by the neuropeptide NLP-1 produced in AWC. In addition, another set of sensory neurons inhibits food-odor preference. These mechanistic logics, together with a previously mapped neural circuit underlying food-odor preference, provide a functional network linking sensory response, transduction, and downstream receptors to process complex olfactory information and generate the appropriate behavioral decision essential for survival.

}, keywords = {*Odors, Animals, Caenorhabditis elegans, Food Preferences/*physiology, Food/classification, Nerve Net/*physiology, Olfactory Receptor Neurons/*physiology, Recognition (Psychology)/*physiology, Smell/*physiology, Synaptic Transmission/*physiology}, isbn = {1529-2401 (Electronic)0270-6474 (Linking)}, author = {* Harris, G. and Shen, Y. and Ha, H. and Donato, A. and Wallis, S. and Zhang, X. and Zhang, Y.} } @article {528661, title = {Dynamic encoding of perception, memory, and movement in a C. elegans chemotaxis circuit ({\textparagraph}: co-first author)}, journal = {^co-corresponding author; Neuron}, volume = {82}, number = {5}, year = {2014}, note = {

Luo, LinjiaoWen, QuanRen, JingHendricks, MichaelGershow, MarcQin, YuqiGreenwood, JoelSoucy, Edward RKlein, MasonSmith-Parker, Heidi KCalvo, Ana CColon-Ramos, Daniel ASamuel, Aravinthan D TZhang, Yuneng1P01GM103770/GM/NIGMS NIH HHS/8DP1GM105383-05/DP/NCCDPHP CDC HHS/P01 GM103770/GM/NIGMS NIH HHS/P01GM103770/GM/NIGMS NIH HHS/P40 OD010440/OD/NIH HHS/R01DC009852/DC/NIDCD NIH HHS/R01NS076558/NS/NINDS NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2014/06/09 06:00Neuron. 2014 Jun 4;82(5):1115-28. doi: 10.1016/j.neuron.2014.05.010.

}, month = {Jun 4}, pages = {1115-28}, abstract = {

Brain circuits endow behavioral flexibility. Here, we study circuits encoding flexible chemotaxis in C. elegans, where the animal navigates up or down NaCl gradients (positive or negative chemotaxis) to reach the salt concentration of previous growth (the set point). The ASER sensory neuron mediates positive and negative chemotaxis by regulating the frequency and direction of reorientation movements in response to salt gradients. Both salt gradients and set point memory are encoded in ASER temporal activity patterns. Distinct temporal activity patterns in interneurons immediately downstream of ASER encode chemotactic movement decisions. Different interneuron combinations regulate positive versus negative chemotaxis. We conclude that sensorimotor pathways are segregated immediately after the primary sensory neuron in the chemotaxis circuit, and sensory representation is rapidly transformed to motor representation at the first interneuron layer. Our study reveals compact encoding of perception, memory, and locomotion in an experience-dependent navigational behavior in C. elegans.

}, keywords = {Animals, Caenorhabditis elegans, Calcium/metabolism, Chemoreceptor Cells/physiology, Chemotaxis/*physiology, Interneurons/physiology, Memory/*physiology, Perception/*physiology}, isbn = {1097-4199 (Electronic)0896-6273 (Linking)}, author = {* Luo, L. and Wen, Q. and Ren, J. and Hendricks, M. and Gershow, M. and Qin, Y. and Greenwood, J. and Soucy, E. R. and Klein, M. and Smith-Parker, H. K. and Calvo, A. C. and Colon-Ramos, D. A. and Samuel, A. D.^ and Zhang, Y.^} } @article {528656, title = {EOL-1, the homolog of the mammalian Dom3Z, regulates olfactory learning in C. elegans}, journal = {J Neurosci}, volume = {34}, number = {40}, year = {2014}, note = {

Shen, YuZhang, JiangwenCalarco, John AZhang, YunengP40 OD010440/OD/NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}t2014/10/03 06:00J Neurosci. 2014 Oct 1;34(40):13364-70. doi: 10.1523/JNEUROSCI.0230-14.2014.

}, month = {Oct 1}, pages = {13364-70}, abstract = {

Learning is an essential function of the nervous system. However, our understanding of molecular underpinnings of learning remains incomplete. Here, we characterize a conserved protein EOL-1 that regulates olfactory learning in Caenorhabditis elegans. A recessive allele of eol-1 (enhanced olfactory learning) learns better to adjust its olfactory preference for bacteria foods and eol-1 acts in the URX sensory neurons to regulate learning. The mammalian homolog of EOL-1, Dom3Z, which regulates quality control of pre-mRNAs, can substitute the function of EOL-1 in learning regulation, demonstrating functional conservation between these homologs. Mutating the residues of Dom3Z that are critical for its enzymatic activity, and the equivalent residues in EOL-1, abolishes the function of these proteins in learning. Together, our results provide insights into the function of EOL-1/Dom3Z and suggest that its activity in pre-mRNA quality control is involved in neural plasticity.

}, keywords = {Analysis of Variance, Animals, Animals, Genetically Modified, Avoidance Learning/drug effects/*physiology, Butanones/adverse effects, Caenorhabditis elegans, Caenorhabditis elegans Proteins/*genetics, Chemotaxis/drug effects/genetics, Green Fluorescent Proteins/genetics/metabolism, Humans, Mice, Mutagenesis, Mutation/genetics, Nuclear Proteins/*genetics/*metabolism, Olfactory Pathways/drug effects/*physiology, RNA Precursors/metabolism, Time Factors}, isbn = {1529-2401 (Electronic)0270-6474 (Linking)}, author = {* Shen, Y. and Zhang, J. and Calarco, J. A. and Zhang, Y.} } @article {528676, title = {An insulin-to-insulin regulatory network orchestrates phenotypic specificity in development and physiology}, journal = {^co-corresponding author; PLoS Genet}, volume = {10}, number = {3}, year = {2014}, note = {

Fernandes de Abreu, Diana AndreaCaballero, AntonioFardel, PascalStroustrup, NicholasChen, ZhunanLee, KyunghwaKeyes, William DNash, Zachary MLopez-Moyado, Isaac FVaggi, FedericoCornils, AstridRegenass, MartinNeagu, AncaOstojic, IvanLiu, ChangCho, YongminSifoglu, DenizShen, YuFontana, WalterLu, HangCsikasz-Nagy, AttilaMurphy, Coleen TAntebi, AdamBlanc, EricApfeld, JavierZhang, YunAlcedo, JoyCh{\textquoteright}ng, QueelimengDP2 OD004402-01/OD/NIH HHS/P40 OD010440/OD/NIH HHS/R01 AG034994/AG/NIA NIH HHS/R01 DC009852/DC/NIDCD NIH HHS/R01AG035317/AG/NIA NIH HHS/R01GM088333/GM/NIGMS NIH HHS/R03 AG032481/AG/NIA NIH HHS/R21EB012803/EB/NIBIB NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2014/03/29 06:00PLoS Genet. 2014 Mar 27;10(3):e1004225. doi: 10.1371/journal.pgen.1004225. eCollection 2014 Mar.

}, month = {Mar}, pages = {e1004225}, abstract = {

Insulin-like peptides (ILPs) play highly conserved roles in development and physiology. Most animal genomes encode multiple ILPs. Here we identify mechanisms for how the forty Caenorhabditis elegans ILPs coordinate diverse processes, including development, reproduction, longevity and several specific stress responses. Our systematic studies identify an ILP-based combinatorial code for these phenotypes characterized by substantial functional specificity and diversity rather than global redundancy. Notably, we show that ILPs regulate each other transcriptionally, uncovering an ILP-to-ILP regulatory network that underlies the combinatorial phenotypic coding by the ILP family. Extensive analyses of genetic interactions among ILPs reveal how their signals are integrated. A combined analysis of these functional and regulatory ILP interactions identifies local genetic circuits that act in parallel and interact by crosstalk, feedback and compensation. This organization provides emergent mechanisms for phenotypic specificity and graded regulation for the combinatorial phenotypic coding we observe. Our findings also provide insights into how large hormonal networks regulate diverse traits.

}, keywords = {Animals, Caenorhabditis elegans Proteins/*genetics, Caenorhabditis elegans/*genetics/growth \& development, Gene Regulatory Networks, Insulin/*genetics/metabolism, Longevity/genetics, Phenotype, Receptor, Insulin/*genetics/metabolism, Signal Transduction/genetics, Somatomedins/genetics/metabolism}, isbn = {1553-7404 (Electronic)1553-7390 (Linking)}, author = {* Fernandes de Abreu, D. A. and Caballero, A. and Fardel, P. and Stroustrup, N. and Chen, Z. and Lee, K. and Keyes, W. D. and Nash, Z. M. and Lopez-Moyado, I. F. and Vaggi, F. and Cornils, A. and Regenass, M. and Neagu, A. and Ostojic, I. and Liu, C. and Cho, Y. and Sifoglu, D. and Shen, Y. and Fontana, W. and Lu, H. and Csikasz-Nagy, A. and Murphy, C. T. and Antebi, A.^ and Blanc, E.^ and Apfeld, J.^ and Zhang, Y.^ and Alcedo, J.^ and Ch{\textquoteright}ng, Q.^} } @article {602931, title = {Quantitative screening of genes regulating tryptophan hydroxylase transcription in Caenorhabditis elegans using microfluidics and an adaptive algorithm.}, journal = {Integrative Biology}, year = {2013}, pages = {372-380}, author = {*Lee, H., and Crane, M.M., and Zhang, Y. and Lu, H.} } @article {528691, title = {Complex RIA calcium dynamics and its function in navigational behavior}, journal = {Worm}, volume = {2}, number = {3}, year = {2013}, note = {

Hendricks, MichaelZhang, Yuneng2014/04/30 06:00Worm. 2013 Jul 1;2(3):e25546. doi: 10.4161/worm.25546. Epub 2013 Jul 12.

}, month = {Jul 1}, pages = {e25546}, abstract = {

Recently, we have reported novel and complex calcium dynamics in the RIA interneuron, which has been implicated in several navigational behaviors in C. elegans. Here, we review our findings on the compartmentalized and global calcium events in RIA and propose functional consequence as well as potential regulatory mechanisms of these intriguing calcium signals.

}, isbn = {2162-4046 (Print)2162-4046 (Linking)}, author = {* Hendricks, M. and Zhang, Y.} } @inbook {528706, title = {Molecular and cellular circuits underlying Caenorhabditis elegans olfactory plasticity}, booktitle = {Invertebrate Learning and Memory}, year = {2013}, publisher = {Elsevier}, organization = {Elsevier}, abstract = {

Caenorhabditis elegans uses olfaction as one of its primary means to sense the quality of its environment throughout its life span. Accordingly, the animal displays experience-dependent plasticity in olfactory sensorimotor responses at different life stages. These various forms of olfactory plasticity include imprinting, adaptation to prolonged odor exposure, conditioning with appetitive or aversive stimuli, and learning to avoid the smells of foods that make it ill. Moreover, a number of these C. elegans olfactory responses are subject to the aging process, as similar responses are in vertebrates. Indeed, the dissection of C. elegans olfactory plasticity has revealed mechanistic underpinnings at molecular, cellular, and circuit levels that show substantial similarities to the mechanisms underlying learning and memory in other animals, including humans.

DOI:\ 10.1016/B978-0-12-415823-8.00010-1

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}, isbn = {B978-0-12-415823-8}, author = {* Alcedo, J. and Zhang, Y.}, editor = {Menzel, Randolf and Benjamin, Paul} } @article {528686, title = {A neuronal signaling pathway of CaMKII and Gqalpha regulates experience-dependent transcription of tph-1}, journal = {J Neurosci}, volume = {33}, number = {3}, year = {2013}, note = {

Qin, YuqiZhang, XiaodongZhang, YunengP40 OD010440/OD/NIH HHS/R01 DC009852/DC/NIDCD NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}t2013/01/18 06:00J Neurosci. 2013 Jan 16;33(3):925-35. doi: 10.1523/JNEUROSCI.2355-12.2013.

}, month = {Jan 16}, pages = {925-35}, abstract = {

Dynamic serotonin biosynthesis is important for serotonin function; however, the mechanisms that underlie experience-dependent transcriptional regulation of the rate-limiting serotonin biosynthetic enzyme tryptophan hydroxylase (TPH) are poorly understood. Here, we characterize the molecular and cellular mechanisms that regulate increased transcription of Caenorhabditis elegans tph-1 in a pair of serotonergic neurons ADF during an aversive experience with pathogenic bacteria, a common environmental peril for worms. Training with pathogenic bacteria induces a learned aversion to the smell of the pathogen, a behavioral plasticity that depends on the serotonin signal from ADF neurons. We demonstrate that pathogen training increases ADF neuronal activity. While activating ADF increases tph-1 transcription, inhibiting ADF activity abolishes the training effect on tph-1, demonstrating the dependence of tph-1 transcriptional regulation on ADF neural activity. At the molecular level, the C. elegans homolog of CaMKII, UNC-43, functions cell-autonomously in ADF neurons to generate training-dependent enhancement in neuronal activity and tph-1 transcription, and this cell-autonomous function of UNC-43 is required for learning. Furthermore, selective expression of an activated form of UNC-43 in ADF neurons is sufficient to increase ADF activity and tph-1 transcription, mimicking the training effect. Upstream of ADF, the Gqalpha protein EGL-30 facilitates training-dependent induction of tph-1 by functional regulation of olfactory sensory neurons, which underscores the importance of sensory experience. Together, our work elucidates the molecular and cellular mechanisms whereby experience modulates tph-1 transcription.

}, keywords = {Animals, Avoidance Learning/physiology, Behavior, Animal/physiology, Caenorhabditis elegans, Caenorhabditis elegans Proteins/*genetics/metabolism, Calcium-Calmodulin-Dependent Protein Kinase Type 2/*genetics/metabolism, Gene Expression Regulation, GTP-Binding Protein alpha Subunits, Gq-G11/*genetics/metabolism, Neurons/*metabolism, Phosphorylation, Serotonin/biosynthesis, Signal Transduction/*physiology, Transcription, Genetic, Tryptophan Hydroxylase/*genetics/metabolism}, isbn = {1529-2401 (Electronic)0270-6474 (Linking)}, author = {* Qin, Y. and Zhang, X. and Zhang, Y.} } @article {528696, title = {Two insulin-like peptides antagonistically regulate aversive olfactory learning in C. elegans}, journal = {Neuron}, volume = {77}, number = {3}, year = {2013}, note = {

Chen, ZhunanHendricks, MichaelCornils, AstridMaier, WolfgangAlcedo, JoyZhang, YunengR01 DC009852/DC/NIDCD NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}t2013/02/12 06:00Neuron. 2013 Feb 6;77(3):572-85. doi: 10.1016/j.neuron.2012.11.025.

}, month = {Feb 6}, pages = {572-85}, abstract = {

The insulin/insulin-like peptides (ILPs) regulate key events in physiology, including neural plasticity. However, the cellular and circuit mechanisms whereby ILPs regulate learning remain largely unknown. Here, we characterize two ILPs that play antagonistic roles in aversive olfactory learning of C. elegans. We show that the ILP ins-6 acts from ASI sensory neurons to enable learning by repressing the transcription of another ILP, ins-7, specifically in URX neurons. A high level of INS-7 from URX disrupts learning by antagonizing the insulin receptor-like homolog DAF-2 in the postsynaptic neurons RIA, which play an essential role in the neural circuit underlying olfactory learning. We also show that increasing URX-generated INS-7 and loss of INS-6, both of which abolish learning, alter RIA neuronal property. Together, our results reveal an "ILP-to-ILP" pathway that links environment-sensing neurons, ASI and URX, to the key neuron, RIA, of a network that underlies olfactory plasticity and modulates its activity.

}, keywords = {Amino Acids/diagnostic use, Analysis of Variance, Animals, Animals, Genetically Modified, Avoidance Learning/drug effects/*physiology, Caenorhabditis elegans, Caenorhabditis elegans Proteins/genetics/metabolism, Calcium/metabolism, Chemotaxis/drug effects/physiology, Choice Behavior/physiology, Dose-Response Relationship, Drug, Embryo, Nonmammalian, Genotype, Green Fluorescent Proteins/genetics, Insulin/*chemistry, Kaplan-Meier Estimate, Mutation/genetics, Odors, Olfactory Pathways/cytology/*physiology, Peptide Hormones/classification/genetics/*physiology, Protein-Serine-Threonine Kinases/genetics/metabolism, Receptor, Insulin/genetics/metabolism, Sensory Receptor Cells/drug effects/physiology, Signal Transduction/drug effects/*physiology, Smell/*drug effects}, isbn = {1097-4199 (Electronic)0896-6273 (Linking)}, author = {* Chen, Z. and Hendricks, M. and Cornils, A. and Maier, W. and Alcedo, J. and Zhang, Y.} } @article {528701, title = {When females produce sperm: genetics of C. elegans hermaphrodite reproductive choice}, journal = {G3 (Bethesda)}, volume = {3}, number = {10}, year = {2013}, note = {

Bahrami, Adam KZhang, YunengResearch Support, Non-U.S. Gov{\textquoteright}tBethesda, Md.2013/08/28 06:00G3 (Bethesda). 2013 Oct 3;3(10):1851-9. doi: 10.1534/g3.113.007914.

}, month = {Oct}, pages = {1851-9}, abstract = {

Reproductive behaviors have manifold consequences on evolutionary processes. Here, we explore mechanisms underlying female reproductive choice in the nematode Caenorhabditis elegans, a species in which females have evolved the ability to produce their own self-fertilizing sperm, thereby allowing these "hermaphrodites" the strategic choice to self-reproduce or outcross with males. We report that hermaphrodites of the wild-type laboratory reference strain N2 favor self-reproduction, whereas a wild isolate CB4856 (HW) favors outcrossing. To characterize underlying neural mechanisms, we show that N2 hermaphrodites deficient in mechanosensation or chemosensation (e.g., mec-3 and osm-6 mutants) exhibit high mating frequency, implicating hermaphrodite perception of males as a requirement for low mating frequency. Within chemosensory networks, we find opposing roles for different sets of neurons that express the cyclic GMP-gated nucleotide channel, suggesting both positive and negative sensory-mediated regulation of hermaphrodite mating frequency. We also show that the ability to self-reproduce negatively regulates hermaphrodite mating. To map genetic variation, we created recombinant inbred lines and identified two QTL that explain a large portion of N2 x HW variation in hermaphrodite mating frequency. Intriguingly, we further show that approximately 40 wild isolates representing C. elegans global diversity exhibit extensive and continuous variation in hermaphrodite reproductive outcome. Together, our findings demonstrate that C. elegans hermaphrodites actively regulate the choice between selfing and crossing, highlight the existence of natural variation in hermaphrodite choice, and lay the groundwork for molecular dissection of this evolutionarily important trait.

}, keywords = {*Self-Fertilization, *Sexual Behavior, Animal, Animals, Caenorhabditis elegans Proteins/genetics/metabolism, Caenorhabditis elegans/*genetics/physiology, Cyclic Nucleotide-Gated Cation Channels/metabolism, Female, Genetic Variation, Hermaphroditic Organisms/*genetics/physiology, LIM-Homeodomain Proteins/genetics/metabolism, Male, Neurons/metabolism/physiology, Neuropeptides/genetics/metabolism, Quantitative Trait Loci, Spermatozoa/physiology, Transcription Factors/genetics/metabolism}, isbn = {2160-1836 (Electronic)2160-1836 (Linking)}, author = {* Bahrami, A. K. and Zhang, Y.} } @article {528716, title = {Compartmentalized calcium dynamics in a C. elegans interneuron encode head movement}, journal = {Nature}, volume = {487}, number = {7405}, year = {2012}, note = {

Hendricks, MichaelHa, HeonickMaffey, NicolasZhang, YunengDC009852/DC/NIDCD NIH HHS/R01 DC009852/DC/NIDCD NIH HHS/R01 DC009852-01A1/DC/NIDCD NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tEngland2012/06/23 06:00Nature. 2012 Jul 5;487(7405):99-103. doi: 10.1038/nature11081.

}, month = {Jul 5}, pages = {99-103}, abstract = {

The confinement of neuronal activity to specific subcellular regions is a mechanism for expanding the computational properties of neurons. Although the circuit organization underlying compartmentalized activity has been studied in several systems, its cellular basis is still unknown. Here we characterize compartmentalized activity in Caenorhabditis elegans RIA interneurons, which have multiple reciprocal connections to head motor neurons and receive input from sensory pathways. We show that RIA spatially encodes head movement on a subcellular scale through axonal compartmentalization. This subcellular axonal activity is dependent on acetylcholine release from head motor neurons and is simultaneously present and additive with glutamate-dependent globally synchronized activity evoked by sensory inputs. Postsynaptically, the muscarinic acetylcholine receptor GAR-3 acts in RIA to compartmentalize axonal activity through the mobilization of intracellular calcium stores. The compartmentalized activity functions independently of the synchronized activity to modulate locomotory behaviour.

}, keywords = {*Calcium Signaling, Acetylcholine/metabolism, Animals, Axons/metabolism, Caenorhabditis elegans/anatomy \& histology/*cytology/*physiology, Calcium/*metabolism, Cell Compartmentation, Glutamic Acid/metabolism, Head Movements/*physiology, Interneurons/*metabolism, Motor Neurons/metabolism, Neural Pathways, Receptors, Muscarinic/metabolism, Synaptic Transmission}, isbn = {1476-4687 (Electronic)0028-0836 (Linking)}, author = {* Hendricks, M. and Ha, H. and Maffey, N. and Zhang, Y.} } @article {528711, title = {DBL-1, a TGF-beta, is essential for Caenorhabditis elegans aversive olfactory learning}, journal = {Proc Natl Acad Sci U S A}, volume = {109}, number = {42}, year = {2012}, note = {

Zhang, XiaodongZhang, YunengR01 DC009852/DC/NIDCD NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}t2012/09/29 06:00Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):17081-6. doi: 10.1073/pnas.1205982109. Epub 2012 Sep 26.

}, month = {Oct 16}, pages = {17081-6}, abstract = {

The TGF-beta superfamily is conserved throughout metazoan, and its members play essential roles in development and disease. TGF-beta has also been implicated in adult neural plasticity. However, the underlying mechanisms are not well understood. Here we report that DBL-1, a Caenorhabditis elegans TGF-beta homolog known to control body morphology and immunity, is essential for aversive olfactory learning of potentially harmful bacteria food. We show that DBL-1 generated by the AVA command interneurons, which are critical for sensorimotor responses, regulates aversive olfactory learning, and that the activity of the type I TGF-beta receptor SMA-6 in the hypodermis is needed during adulthood to generate olfactory plasticity. These spatial and temporal mechanisms are critical for the DBL-1 signaling to achieve its diverse functions in development and adult neural plasticity. Interestingly, aversive training decreases AVA calcium response, leading to an increase in the DBL-1 signal secreted from AVA, revealing an experience-dependent change that can underlie the role of TGF-beta signaling in mediating plasticity.

}, keywords = {Animals, Avoidance Learning/*physiology, Caenorhabditis elegans Proteins/*metabolism, Caenorhabditis elegans/*physiology, Interneurons/metabolism, Microscopy, Fluorescence, Neuronal Plasticity/physiology, Neuropeptides/*metabolism, Receptors, Cell Surface/metabolism, Smell/*physiology, Transforming Growth Factor beta/*metabolism}, isbn = {1091-6490 (Electronic)0027-8424 (Linking)}, author = {* Zhang, X. and Zhang, Y.} } @article {528721, title = {Specific insulin-like peptides encode sensory information to regulate distinct developmental processes}, journal = {Development}, volume = {138}, number = {6}, year = {2011}, note = {

Cornils, AstridGloeck, MarioChen, ZhunanZhang, YunAlcedo, JoyengR01 DC009852/DC/NIDCD NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tEnglandCambridge, England2011/02/24 06:00Development. 2011 Mar;138(6):1183-93. doi: 10.1242/dev.060905.

}, month = {Mar}, pages = {1183-93}, abstract = {

An insulin-like signaling pathway mediates the environmental influence on the switch between the C. elegans developmental programs of reproductive growth versus dauer arrest. However, the specific role of endogenous insulin-like peptide (ILP) ligands in mediating the switch between these programs remains unknown. C. elegans has 40 putative insulin-like genes, many of which are expressed in sensory neurons and interneurons, raising the intriguing possibility that ILPs encode different environmental information to regulate the entry into, and exit from, dauer arrest. These two developmental switches can have different regulatory requirements: here we show that the relative importance of three different ILPs varies between dauer entry and exit. Not only do we find that one ILP, ins-1, ensures dauer arrest under harsh environments and that two other ILPs, daf-28 and ins-6, ensure reproductive growth under good conditions, we also show that daf-28 and ins-6 have non-redundant functions in regulating these developmental switches. Notably, daf-28 plays a more primary role in inhibiting dauer entry, whereas ins-6 has a more significant role in promoting dauer exit. Moreover, the switch into dauer arrest surprisingly shifts ins-6 transcriptional expression from a set of dauer-inhibiting sensory neurons to a different set of neurons, where it promotes dauer exit. Together, our data suggest that specific ILPs generate precise responses to dauer-inducing cues, such as pheromones and low food levels, to control development through stimulus-regulated expression in different neurons.

}, keywords = {Animals, Animals, Genetically Modified, Caenorhabditis elegans Proteins/genetics/metabolism/physiology, Caenorhabditis elegans/*embryology/genetics/*growth \& development/metabolism, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Insulin/chemistry/genetics/metabolism/physiology, Longevity/genetics/physiology, Peptide Fragments/genetics/metabolism/physiology, Peptide Hormones/chemistry/genetics/metabolism/physiology, Receptor, Insulin/genetics/metabolism/physiology, Signal Transduction, Somatomedins/genetics/metabolism/*physiology, Survival/physiology}, isbn = {1477-9129 (Electronic)0950-1991 (Linking)}, author = {Cornils, A. and Gloeck, M. and Chen, Z. and Zhang, Y. and Alcedo, J.} } @article {528726, title = {Functional organization of a neural network for aversive olfactory learning in Caenorhabditis elegans}, journal = {Neuron}, volume = {68}, number = {6}, year = {2010}, note = {

Ha, Heon-ickHendricks, MichaelShen, YuGabel, Christopher VFang-Yen, ChristopherQin, YuqiColon-Ramos, DanielShen, KangSamuel, Aravinthan D TZhang, Yuneng4R00NS57931/NS/NINDS NIH HHS/R01 DC009852/DC/NIDCD NIH HHS/R01 DC009852-01A1/DC/NIDCD NIH HHS/Howard Hughes Medical Institute/Comparative StudyResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2010/12/22 06:00Neuron. 2010 Dec 22;68(6):1173-86. doi: 10.1016/j.neuron.2010.11.025.

}, month = {Dec 22}, pages = {1173-86}, abstract = {

Many animals use their olfactory systems to learn to avoid dangers, but how neural circuits encode naive and learned olfactory preferences, and switch between those preferences, is poorly understood. Here, we map an olfactory network, from sensory input to motor output, which regulates the learned olfactory aversion of Caenorhabditis elegans for the smell of pathogenic bacteria. Naive animals prefer smells of pathogens but animals trained with pathogens lose this attraction. We find that two different neural circuits subserve these preferences, with one required for the naive preference and the other specifically for the learned preference. Calcium imaging and behavioral analysis reveal that the naive preference reflects the direct transduction of the activity of olfactory sensory neurons into motor response, whereas the learned preference involves modulations to signal transduction to downstream neurons to alter motor response. Thus, two different neural circuits regulate a behavioral switch between naive and learned olfactory preferences.

}, keywords = {Animals, Avoidance Learning/drug effects/*physiology, Bacterial Proteins/toxicity, Caenorhabditis elegans/*physiology, Motor Activity/drug effects/*physiology, Nerve Net/drug effects/*physiology, Olfactory Pathways/drug effects/*physiology, Smell/drug effects/*physiology}, isbn = {1097-4199 (Electronic)0896-6273 (Linking)}, author = {* Ha, H. I. and Hendricks, M. and Shen, Y. and Gabel, C. V. and Fang-Yen, C. and Qin, Y. and Colon-Ramos, D. and Shen, K. and Samuel, A. D. and Zhang, Y.} } @article {528741, title = {Olfactory behavior of swimming C. elegans analyzed by measuring motile responses to temporal variations of odorants}, journal = {J Neurophysiol}, volume = {99}, number = {5}, year = {2008}, note = {

Luo, LinjiaoGabel, Christopher VHa, Heon-IckZhang, YunSamuel, Aravinthan D TengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2008/03/28 09:00J Neurophysiol. 2008 May;99(5):2617-25. doi: 10.1152/jn.00053.2008. Epub 2008 Mar 26.

}, month = {May}, pages = {2617-25}, abstract = {

Caenorhabditis elegans responds to chemical cues using a small number of chemosensory neurons that detect a large variety of molecules in its environment. During chemotaxis, C. elegans biases its migration in spatial chemical gradients by lengthening (/shortening) periods of forward movement when it happens to be moving toward (/away) from preferred locations. In classical assays of chemotactic behavior, a group of crawling worms is placed on an agar plate containing a point source of chemical, the group is allowed to navigate for a period of time, and aggregation of worms near the source is quantified. Here we show that swimming worms exhibit acute motile responses to temporal variations of odor in their surrounding environment, allowing our development of an automated assay of chemotactic behavior with single-animal resolution. By placing individual worms in small microdroplets and quantifying their movements as they respond to the addition and removal of odorized airstreams, we show that the sensorimotor phenotypes of swimming worms (wild-type behavior, the effects of certain mutations, and the effects of laser ablation of specific olfactory neurons) are consistent with aggregation phenotypes previously obtained in crawling assays. The microdroplet swimming assay has certain advantages over crawling assays, including flexibility and precision in defining the stimulus waveform and automated quantification of motor response during stimulus presentation. In this study, we use the microdroplet assay to quantify the temporal dynamics of the olfactory response, the sensitivity to odorant concentration, combinations, and gradients, and the contribution of specific olfactory neurons to overall behavior.

}, keywords = {*Odors, Animals, Behavior, Animal/*physiology, Caenorhabditis elegans/*physiology, Dose-Response Relationship, Drug, Lasers, Mutation/physiology, Neurons, Afferent/physiology, Pentanols, Smell/*physiology, Swimming/*physiology}, isbn = {0022-3077 (Print)0022-3077 (Linking)}, author = {Luo, L. and Gabel, C. V. and Ha, H. I. and Zhang, Y. and Samuel, A. D.} } @article {528746, title = {Detection and avoidance of a natural product from the pathogenic bacterium Serratia marcescens by Caenorhabditis elegans {\textparagraph}: co-first author}, journal = {Proc Natl Acad Sci U S A}, volume = {104}, number = {7}, year = {2007}, note = {

Pradel, ElizabethZhang, YunPujol, NathalieMatsuyama, ToheyBargmann, Cornelia IEwbank, Jonathan JengWellcome Trust/United KingdomResearch Support, Non-U.S. Gov{\textquoteright}t2007/02/03 09:00Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2295-300. Epub 2007 Jan 31.

}, month = {Feb 13}, pages = {2295-300}, abstract = {

The nematode Caenorhabditis elegans is present in soils and composts, where it can encounter a variety of microorganisms. Some bacteria in these rich environments are innocuous food sources for C. elegans, whereas others are pathogens. Under laboratory conditions, C. elegans will avoid certain pathogens, such as Serratia marcescens, by exiting a bacterial lawn a few hours after entering it. By combining bacterial genetics and nematode genetics, we show that C. elegans specifically avoids certain strains of Serratia based on their production of the cyclic lipodepsipentapeptide serrawettin W2. Lawn-avoidance behavior is chiefly mediated by the two AWB chemosensory neurons, probably through G protein-coupled chemoreceptors, and also involves the nematode Toll-like receptor gene tol-1. Purified serrawettin W2, added to an Escherichia coli lawn, can directly elicit lawn avoidance in an AWB-dependent fashion, as can another chemical detected by AWB. These findings represent an insight into chemical recognition between these two soil organisms and reveal sensory mechanisms for pathogen recognition in C. elegans.

}, keywords = {Animals, Avoidance Learning/*drug effects, Biological Products/pharmacology/secretion, Caenorhabditis elegans Proteins/physiology, Caenorhabditis elegans/*microbiology/*physiology, Lipoproteins/*pharmacology/secretion, Nerve Tissue Proteins/physiology, Peptides, Cyclic/*pharmacology/secretion, Serratia marcescens/*chemistry}, isbn = {0027-8424 (Print)0027-8424 (Linking)}, author = {Pradel, E.{\textparagraph} and Zhang, Y.{\textparagraph} and Pujol, N. and Matsuyama, T. and Bargmann, C. I. and Ewbank, J. J.} } @article {528751, title = {Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans}, journal = {Nature}, volume = {438}, number = {7065}, year = {2005}, note = {

Zhang, YunLu, HangBargmann, Cornelia IengResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, P.H.S.England2005/11/11 09:00Nature. 2005 Nov 10;438(7065):179-84.

}, month = {Nov 10}, pages = {179-84}, abstract = {

Food can be hazardous, either through toxicity or through bacterial infections that follow the ingestion of a tainted food source. Because learning about food quality enhances survival, one of the most robust forms of olfactory learning is conditioned avoidance of tastes associated with visceral malaise. The nematode Caenorhabditis elegans feeds on bacteria but is susceptible to infection by pathogenic bacteria in its natural environment. Here we show that C. elegans modifies its olfactory preferences after exposure to pathogenic bacteria, avoiding odours from the pathogen and increasing its attraction to odours from familiar nonpathogenic bacteria. Particular bacteria elicit specific changes in olfactory preferences that are suggestive of associative learning. Exposure to pathogenic bacteria increases serotonin in ADF chemosensory neurons by transcriptional and post-transcriptional mechanisms. Serotonin functions through MOD-1, a serotonin-gated chloride channel expressed in sensory interneurons, to promote aversive learning. An increase in serotonin may represent the negative reinforcing stimulus in pathogenic infection.

}, keywords = {Animals, Bacteria/isolation \& purification/*pathogenicity, Caenorhabditis elegans Proteins/metabolism, Caenorhabditis elegans/genetics/*microbiology/*physiology, Chloride Channels/metabolism, Diet, Food Preferences/*physiology, Interneurons/metabolism, Learning/*physiology, Maze Learning/physiology, Odors/*analysis, Serotonin/metabolism, Smell/*physiology}, isbn = {1476-4687 (Electronic)0028-0836 (Linking)}, author = {Zhang, Y. and Lu, H. and Bargmann, C. I.} } @article {528756, title = {Identification of genes expressed in C. elegans touch receptor neurons}, journal = {Nature}, volume = {418}, number = {6895}, year = {2002}, note = {

Zhang, YunMa, CharlesDelohery, ThomasNasipak, BrianFoat, Barrett CBounoutas, AlexanderBussemaker, Harmen JKim, Stuart KChalfie, MartinengR37 GM030997/GM/NIGMS NIH HHS/Research Support, U.S. Gov{\textquoteright}t, P.H.S.England2002/07/19 10:00Nature. 2002 Jul 18;418(6895):331-5.

}, month = {Jul 18}, pages = {331-5}, abstract = {

The extent of gene regulation in cell differentiation is poorly understood. We previously used saturation mutagenesis to identify 18 genes that are needed for the development and function of a single type of sensory neuron--the touch receptor neuron for gentle touch in Caenorhabditis elegans. One of these genes, mec-3, encodes a transcription factor that controls touch receptor differentiation. By culturing and isolating wild-type and mec-3 mutant cells from embryos and applying their amplified RNA to DNA microarrays, here we have identified genes that are known to be expressed in touch receptors, a previously uncloned gene (mec-17) that is needed for maintaining touch receptor differentiation, and more than 50 previously unknown mec-3-dependent genes. These genes are randomly distributed in the genome and under-represented both for genes that are co-expressed in operons and for multiple members of gene families. Using regions 5{\textquoteright} of the start codon of the first 20 genes, we have also identified an over-represented heptanucleotide, AATGCAT, that is needed for the expression of touch receptor genes.

}, keywords = {Amino Acid Sequence, Animals, Base Sequence, Caenorhabditis elegans Proteins/*genetics, Caenorhabditis elegans/*cytology/*genetics, Cell Differentiation, Cell Size, Cloning, Molecular, Flow Cytometry, Gene Expression Profiling, Genes, Helminth/*genetics, Helminth Proteins/genetics/metabolism, LIM-Homeodomain Proteins, Molecular Sequence Data, Mutation, Neurons, Afferent/cytology/*metabolism, Oligonucleotide Array Sequence Analysis, Response Elements/genetics, Reverse Transcriptase Polymerase Chain Reaction, RNA, Helminth/genetics/metabolism, RNA, Messenger/genetics/metabolism, Touch/*physiology, Transcription Factors}, isbn = {0028-0836 (Print)0028-0836 (Linking)}, author = {Zhang, Y. and Ma, C. and Delohery, T. and Nasipak, B. and Foat, B. C. and Bounoutas, A. and Bussemaker, H. J. and Kim, S. K. and Chalfie, M.} } @article {528761, title = {MTD-1, a touch-cell-specific membrane protein with a subtle effect on touch sensitivity}, journal = {Mech Dev}, volume = {119}, number = {1}, year = {2002}, note = {

Zhang, YunChalfie, MartinengGM 30997/GM/NIGMS NIH HHS/R37 GM030997/GM/NIGMS NIH HHS/Research Support, U.S. Gov{\textquoteright}t, P.H.S.Ireland2002/10/19 04:00Mech Dev. 2002 Nov;119(1):3-7.

}, month = {Nov}, pages = {3-7}, abstract = {

We have used representational difference analysis (RDA) applied to cDNA to isolate transcripts regulated by MEC-3, a transcription factor needed for the differentiation of the six touch receptor neurons in Caenorhabditis elegans. Six percent of 595 cDNAs isolated by cDNA RDA were mec-3-dependent. These cDNAs represented mRNA from two previously known genes, mec-18 and mec-7, and one new gene, mtd-1 (mec-three-dependent). mtd-1 encodes a novel transmembrane protein that is exclusively expressed in the six touch cells throughout development. mtd-1 loss results in a subtle defect in the touch receptor neurons. Neither mtd-1 RNAi nor a putative mtd-1 loss-of-function mutation resulted in touch insensitivity, but both enhanced the touch insensitivity of mec-6(u247), a temperature sensitive allele, at the permissive temperature.

}, keywords = {Alleles, Amino Acid Sequence, Animals, Blotting, Northern, Blotting, Southern, Caenorhabditis elegans Proteins/genetics/*metabolism/*physiology, Caenorhabditis elegans/metabolism, Cell Membrane/*metabolism, DNA, Complementary/metabolism, Gene Deletion, Gene Expression Regulation, Homozygote, LIM-Homeodomain Proteins, Membrane Proteins/genetics/*metabolism/*physiology, Molecular Sequence Data, Mutation, Neurons/metabolism, Phenotype, RNA, Double-Stranded/metabolism, Temperature, Touch, Transcription Factors/metabolism/physiology, Ultraviolet Rays}, isbn = {0925-4773 (Print)0925-4773 (Linking)}, author = {Zhang, Y. and Chalfie, M.} }