1,720,964 research outputs found
Mechanisms of NPY Y2 Receptor-Mediated Anxiogenesis in the Basolateral Amygdala
Full text linkFear and anxiety are highly adaptive emotions that motivate species appropriate responses to threats: immediate and potential. Certain threats, such as ancestral predators, are highly predictable and can be recognized and addressed with innate (inherited) neural systems. This “genetic memory” underlies human phobias (ex. fear of snakes) and allows individuals to recognize and effectively respond to conserved dangers, regardless of previous encounters. Unlearned fear systems, however, have clear limitations, the most fundamental being their inability to recognize every conceivable danger. Plastic threat appraisal systems overcome this limitation. The basolateral amygdala (BLA) is the principal brain site where learned associations between innocuous sensory cues and intrinsically aversive stimuli are formed (fear conditioning). Fear conditioning is though to model a key mechanism for identifying novel threats. Anxiety, a more sustained state of hyper-vigilance, is also mediated by the BLA and is most appropriate when threats are diffuse and not readily predicted by explicit cues. In susceptible individuals, exposure to a severe unpredictable stressor can elicit a prolonged disordered anxiety state termed posttraumatic stress disorder (PTSD). Although protective to a degree, PTSD substantially impairs normal functioning and is profoundly unpleasant for the sufferer. An important factor thought to protect some individuals from the deleterious effects of traumatic stress is Neuropeptide Y (NPY). BLA NPY infusions are highly anxiolytic in rodents, while repeated infusions produce plastic changes culminating in a long lasting low-anxiety state. Glutamatergic Principal neurons (PN) are the BLA’s majority neuron type (85%) and mediate its output. The remaining 15% are a diverse group of GABA interneurons that tightly regulate PN activity. The output of a population PNs signals fear and anxiety. We previously showed that NPY inhibits BLA PNs via postsynaptic NPY Y1 receptors (consistent with anxiolytic actions). Furthermore, Y1 selective agonists mimic NPYs acute in vivo anxiolytic effects. Surprisingly, selective activation of BLA Y2 receptors (Y2-R) increases anxiety by an (until now) unknown mechanism. The principal focus of this thesis is to mechanistically dissect Y2-R functions in the BLA. A secondary aim is to determine if and how Y2-Rs contribute to the overall anxiolytic actions of the full agonist NPY. Y2-Rs are typically presynaptic and inhibit neurotransmitter release. We therefore, hypothesized Y2-Rs disinhibit PNs by decreasing BLA interneuron GABA release. To test this, we used slice-patch electrophysiology in rat BLA-containing brain slices. Application of the selective Y2-R agonist [ahx5-24]NPY decreased the frequency of PN miniature GABAA inhibitory postsynaptic currents (IPSC)s with no effect on amplitude (suggesting a presynaptic effect). Interestingly, in the absence of tetrodotoxin (TTX) [ahx5-24]NPY increased the frequency of large amplitude fast kinetic sIPSCs, suggesting disinhibition of another interneuron type. To determine the Y2-R expressing interneuron type mediating the above effects, we used a mouse model engineered to express the TdTomato fluorophore under control of the Y2-R gene promoter. Immunohistochemistry studies suggested Y2-Rs are expressed exclusively on interneurons characterized by NPY and somatostatin (SOM) expression. SOM interneurons innervate PN dendrites and also target other interneuron types consistent with electrophysiology findings. In addition to the above effects, [ahx5-24]NPY increased PN excitability (indicated by a decrease in the depolarizing current required to elicit action potentials). These findings are consistent with the in vivo anxiogenic effects of selective Y2-R agonists. Although [ahx5-24]NPY only slightly depolarized most PNs, it substantially increased PN input resistance, indicating a net closure of ion channels. We hypothesized these effects were due to reduced tonic GABAA-mediated inhibition. However voltage-clamp experiments indicated [ahx5-24]NPY reduced a PN G-protein coupled inward rectifying K+ conductance (GIRK). Subsequent experiments revealed this was due to reduced tonic GABAB-R activation. Since PNs express postsynaptic GABAB-Rs exclusively at their dendrites this effect is also consistent with actions on (Y2-R expressing) NPY/SOM interneurons. Surprisingly, this Y2-R action persisted in TTX, indicating it is largely action potential-independent. Ultimately this finding reveals a highly novel consequence of action potential-independent neurotransmission. NPY-mediated plasticity requires the Ca2+-dependent phosphatase calcineurin (which mediates LTD-type learning and is expressed in dendrites). Dendritic GABAB-GIRKs facilitate the Mg2+ block of NMDA receptors and dampen plasticity. Thus Y2-Rs may function to disinhibit PN dendrites and facilitate Ca2+-dependent, NPY-mediated plasticity. [ahx5-24]NPY-mediated increases in PN calcium influx were revealed indirectly by an increase Ca2+ dependent slow after-hyperpolarization (sIAHP) K+ current in half of all responsive PNs
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Neuronal and synaptic organization, and central afferent and efferent organization of the gravity receptor system of the statocyst of Octopus vulgaris
No full textkoamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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