1,720,994 research outputs found
Electrophysiological study of dopamine neurons in the dorsal raphe nucleus & ventrolateral periaqueductal grey
Get PDFThe midbrain dopamine system plays a fundamental conserved role in regulating behaviour, and its dysfunction is associated with several neuropsychiatric disorders including addiction, schizophrenia, and Parkinson’s Disease. Midbrain dopamine neurons display considerable heterogeneity in their neurochemical, electrophysiological, and functional properties, and project to many cortical and subcortical structures. The majority of these neurons reside within the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA), but a less well-known, and understudied, dopamine population are housed within the dorsal raphe nucleus (DRN) and ventrolateral periaqueductal grey (vlPAG). These neurons provide the majority of the dopaminergic input to the central extended amygdala and have been implicated in the sleep-wake cycle and mediating the effects of opiates. However, their electrophysiological properties have not been examined. I have studied these neurons in mice using immunohistochemistry and electrophysiology in an acute brain slice preparation ex vivo. I found that they display similar properties to some VTA dopamine neurons, and noted co-expression of vasoactive intestinal peptide in a subset of this population. A characteristic feature of VTA dopamine neurons is the potentiation observed at glutamatergic synapses following a single dose of addictive drug or an acute stress experience. I investigated whether DRN/vlPAG dopamine neurons would show cocaine-induced plasticity and found that glutamatergic synapses were potentiated not only by a single dose of cocaine, but also by acute social isolation. This potentiation was associated with a change in AMPAR transmission, which is similar to that observed following cocaine in the VTA. I also investigated the hypothesis that this plasticity is a result of acute anxiety using behavioural analysis and administration of anxiolytic compounds. These findings suggest another form of salient stimulus which can induce plasticity in dopamine neurons, and have relevance to several neuropsychiatric diseases including those modelled by social isolation
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Assessing changes induced by in utero low protein dietary exposure in offspring development and behaviour
Get PDFEmbryonic development involves temporal and spatial coordination of epigenetic processes,
which are exquisitely sensitive to environmental influences and can have life-long implications
for disease if disrupted. In this thesis, I examined the impact of gestational diet, specifically protein
restriction, on the expression of cyclin-dependent kinase inhibitor C1 (Cdkn1c), a gene that
is epigenetically regulated through genomic imprinting, during development and post-natally,
with an allele-specific bioluminescent reporter mouse model. I showed that in utero low protein
diet (LPD) exposure affects behaviour in adolescence and adulthood, through changes in the
dopamine system at a transcriptional, cellular and metabolic level. Sensitisation experiments
suggest that adult LPD mice are hypersensitive to cocaine, as they show increased locomotor
activity compared to controls, and increased stereotypy at higher doses. Adult LPD mice also
show hyperactivity and reduced anxiety, which are phenotypes frequently observed in hyperdopaminergic
mouse models. Adolescent LPD mice demonstrated impaired motor function, in
contrast to age-matched controls, based on open field and rotarod performance. However, I have
shown this deficit to be transient and resolved by adulthood. Juvenile and adult LPD-exposed
mice displayed a 25% increase in midbrain dopaminergic neuron numbers. Moreover, RNA
analysis from adult midbrains showed a downregulation of the gene that encodes dopamine
transporter (DAT) and upregulation of dopamine receptor 5 (D5) in LPD mice, with many
other dopamine-related genes unaffected. A pilot RNA-seq experiment on midbrain neuronal
nuclei identified 123 differentially expressed genes in LPD mice, affecting cholesterol synthesis
and markers linked to neurodegeneration and early-life stress. Lastly, μPET imaging revealed
elevated striatal dopamine synthesis capacity in adult LPD mice, recapitulating one of the
hallmarks of schizophrenia, and in accordance with reports of gestational exposure to famine
inferring increased susceptibility to schizophrenia. This work sheds light on consequences of
early-life adversity and epigenetic disruption on embryonic brain development, behaviour and
disease risk.Open Acces
Investigating reward systems in the human midbrain with fMRI
Get PDFLocalising activity in the human midbrain with conventional functional MRI
(fMRI) is challenging because the midbrain nuclei are small and located in an
area that is prone to physiological artefacts. In the first section of this thesis I
present a replicable and automated method to improve the detection and
localisation of midbrain fMRI signals. I designed a visual fMRI task that was
predicted would activate the superior colliculi bilaterally. A novel anatomical
registration pathway was used to optimise the localisation of the small
midbrain nuclei in stereotactic space. This pathway was compared to
conventional registration pathways, and was shown to significantly improve
midbrain registration. To reduce the physiological artefacts in the functional
data, I estimated and removed structured noise using a modified version of a
previously described physiological noise model (PNM). Whereas a
conventional analysis revealed only unilateral colliculi activity, the PNM
analysis revealed the predicted bilateral activity.
I then used these methods to investigate the role of the midbrain
dopaminergic system in reward. Midbrain dopamine neurons play central
roles in positive reward prediction errors (PEs). Non-human studies now
indicate that dopamine neurons also code for aversive, punishing events, and
may code negative PEs. However, our understanding of how such events are
coded in the human dopaminergic midbrain is limited, and has been hindered
by the technical challenge of using fMRI in this region. Here I show that during
a financial reward and punishment task the ventral tegmental area (VTA)
codes for both positive and negative PEs. The fMRI data from the midbrain
contained a significant amount of physiological noise, but once I applied the
PNM responses were also observed in the substantia nigra pars compacta
(SNc), with negative PE signals extending more laterally. These findings
indicate that both the human VTA and SNc code for both positive and
negative PEs
Variations on the Author
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/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
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