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Studies on the actions of the nematode FMRFamide like neuropeptide PF1
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Metabotropic glutamate receptors: modulators of context-dependent feeding behaviour in C. elegans.
No full textGlutamatergic neurotransmission is evolutionarily conserved across animal phyla. A major class of glutamate receptors are the metabotropic glutamate receptors (mGluRs). In C. elegans three mGluR genes mgl-1, mgl-2 and mgl-3 are organised into three sub-groups, similar to their mammalian counterparts. Cellular reporters identified expression of the mgls in the nervous system of C. elegans and overlapping expression in the pharyngeal microcircuit that controls pharyngeal muscle activity and feeding behaviour. The overlapping expression of mgls within this circuit allowed investigation of receptor signalling per se and in the context of receptor interactions within a neural network that regulates feeding. We utilized the pharmacological manipulation of neuronally regulated pumping of the pharyngeal muscle in wild type and mutants to investigate mgl function. This defined a net mgl-1 dependent inhibition of pharyngeal pumping which is modulated by mgl-3 excitation. Optogenetic activation of the pharyngeal glutamatergic inputs combined with electrophysiological recordings from the isolated pharyngeal preparations provided further evidence for a presynaptic mgl-1 dependent regulation of pharyngeal activity. Analysis of mgl-1, mgl-2 and mgl-3 mutant feeding behaviour in the intact organism after acute food removal identified a significant role for mgl-1 in the regulation of an adaptive feeding response. Our data describes the molecular and cellular organisation of mgl-1, mgl-2 and mgl-3. Pharmacological analysis identified that in these paradigms mgl-1 and mgl-3, but not mgl-2, can modulate the pharyngeal microcircuit. Behavioural analysis identified mgl-1 as a significant determinant of the glutamate-dependent modulation of feeding, further highlighting the significance of mGluRs in complex C. elegans behaviour
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Role of a FMRFamide-like family of neuropeptides in the pharyngeal nervous system of Caenorhabditis elegans
No full textThe nervous system of C. elegans has a remarkable abundance of flp genes encoding FMRFamide-like (FLP) neuropeptides. To provide insight into the physiological relevance of this neuropeptide diversity, we have tested more than 30 FLPs (encoded by 23 flps) for bioactivity on C. elegans pharynx. Eleven flp genes encode peptides that inhibit pharyngeal activity, while eight flp genes encode peptides that are excitatory. Three potent peptides (inhibitory, FLP-13A, APEASPFIRFamide; excitatory, FLP-17A, KSAFVRFamide; excitatory, FLP-17B, KSQYIRFamide) are encoded by flp genes, which, according to reporter gene constructs, are expressed in pharyngeal motoneurons. Thus, they may act through receptors localized on the pharyngeal muscle. The two other potent peptides, FLP-8 (excitatory AF1, KNEFIRFamide,) and FLP-11A (inhibitory, AMRNALVRFamide), appear to be expressed in extrapharyngeal neurons and are therefore likely to act either indirectly or as neurohormones. Intriguingly, a single neuron can express peptides that have potent but opposing biological activity in the pharynx. Only five flp genes encode neuropeptides that have no observable effect on the pharynx, but none of these have shown reporter gene expression in the pharyngeal nervous system. To examine the roles of multiple peptides produced from single precursors, a comparison was made between the bioactivity of different neuropeptides for five flp genes (flp-3, flp-13, flp-14, flp-17, and flp-18). For all but one gene (flp-14), the effects of peptides encoded by the same gene were similar. Overall, this study demonstrates the impressive neurochemical complexity of the simple circuit that regulates feeding in the nematode, C. elegans. © 2005 Wiley Periodicals, Inc. J Neurobiol, 200
Characterization of glutamate-gated chloride channels in the pharynx of wild-type and mutant Caenorhabditis elegans delineates the role of the subunit GluCl-alpha 2 in the function of the native receptor
No full textGlutamate-gated chloride (GluCl) channels are the site of action of the anthelmintic ivermectin. Previously, the Xenopus laevis oocyte expression system has been used to characterize GluCl channels cloned from Caenorhabditis elegans. However, information on the native, pharmacologically relevant receptors is lacking. Here, we have used a quantitative pharmacological approach and intracellular recording techniques of C. elegans pharynx to characterize them. The glutamate response was a rapidly desensitizing, reversible, chloride-dependent depolarization (EC50 = 166 µM), only weakly antagonized by picrotoxin. The order of potency of agonists was ibotenate > L-glutamate > kainate = quisqualate. Ivermectin potently and irreversibly depolarized the muscle (EC50 = 2.7 nM). No further depolarization was seen with coapplication of maximal glutamate during the maximal ivermectin response, indicating that ivermectin depolarizes the muscle by the same ionic mechanism as glutamate (i.e., chloride). The potency of ivermectin on the pharynx was greater than at any of the GluCl subunits expressed in X. laevis oocytes. This effect of ivermectin was abolished in the mutant avr-15, which lacks a functional GluCl-alpha 2 subunit. However, a chloride-dependent, nondesensitizing response to glutamate persisted. Therefore, the GluCl-alpha 2 subunit confers ivermectin sensitivity and a high-affinity desensitizing glutamate response on the native pharyngeal GluCl receptor
A comparison of electrically evoked and channel rhodopsin-evoked postsynaptic potentials in the pharyngeal system of Caenorhabditis elegans
No full textDissecting the function of neural circuits requires the capability to stimulate and record from the component neurones. Optimally, the methods employed should enable precise activation of distinct elements within the circuit and high-fidelity readout of the neuronal response. Here we compare two methods for neural stimulation in the pharyngeal system of Caenorhabditis elegans by evoking postsynaptic potentials (PSPs) either by electrical stimulation or by expression of the channelrhodopsin [ChR2(gf)] in cholinergic neurones of the pharyngeal circuit. Using a dissection that isolates the pharynx and its embedded neural system of 20 neurones permits analysis of the neurotransmitter pathways within this microcircuit. We describe protocols for selective electrically evoked or ChR2-mediated cholinergic synaptic events in this circuit. The latter was achieved by generating strains, punc-17::ChR2(gf);yfp, that express ChR2(gf) in cholinergic neurones. PSPs evoked by both electrical and light stimulation exhibited a rapid time-course and were blocked by cholinergic receptor antagonists and rapidly reversed on cessation of the stimulus. Electrically evoked PSPs were also reduced in a hypomorphic mutant for the synaptic vesicle acetylcholine transporter, unc-17, further indicating they are nicotinic cholinergic PSPs. The pharyngeal nervous system is exquisitely sensitive to both electrical and light activation. For the latter, short light pulses of 200 ?s delivered to punc-17::ChR2(gf);yfp are capable of generating full muscle action potentials. We conclude that the application of optogenetic approaches to the C. elegans isolated pharynx preparation opens the way for a precise molecular dissection of synaptic events in the pharyngeal microcircuit by providing a molecular and system level analysis of the synapses that control the feeding behaviour of C. elegans
Anatomy, physiology and pharmacology of Caenorhabditis elegans pharynx: a model to define gene function in a simple neural system
No full textInvertebrate neuroscience has provided a number of very informative model systems that have been extensively utilized in order to define the neurobiological bases of animal behaviours (Sattelle and Buckingham in Invert Neurosci 6:1–3, 2006). Most eminent among these are a number of molluscs, including Aplysia californica, Lymnaea stagnalis and Helix aspersa, crustacean systems such as the crab stomatogastric ganglion and a wide-range of other arthropods. All of these have been elegantly exploited to shed light on the very important phenomenon of the molecular and cellular basis for synaptic regulation that underpins behavioural plasticity. Key to the successful use of these systems has been the ability to study well-defined, relatively simple neuronal circuits that direct and regulate a quantifiable animal behaviour. Here we describe the pharyngeal system of the nematode C. elegans and its utility as a model for defining the genetic basis of behaviour. The circuitry of the nervous system in this animal is uniquely well-defined. Furthermore, the feeding behaviour of the worm is controlled by the activity of the pharynx and this in turn is regulated in a context-dependent manner by a simple nervous system that integrates external signals, e.g. presence or absence of food, and internal signals, e.g. the nutritional status of the animal to direct an appropriate response. The genetics of C. elegans is being effectively exploited to provide novel insight into genes that function to regulate the neuronal network that controls the pharynx. Here we summarise the progress to date and highlight topics for future research. Two main themes emerge. First, although the anatomy of the pharyngeal system is very well-defined, there is a much poorer understanding of its neurochemistry. Second, it is evident that the neurochemistry is remarkably complex for such a simple circuit/behaviour. This suggests that the pharyngeal activity may be subject to exquisitely precise regulation depending on the animal’s environment and status. This therefore provides a very tractable genetic model to investigate neural mechanisms for signal integration and synaptic plasticity in a well-defined neuronal network that directs a quantifiable behaviour, feeding
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