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Localization and contribution of voltage-gated calcium channels in retinal ganglion cells and their unmyelinated axons
Get PDFABSTRACT OF DISSERTATIONLocalization and contribution of voltage-gated calcium channels in retinal ganglion cells and their unmyelinated axonsbyAllison Michelle SargoyDoctor of Philosophy in NeurobiologyUniversity of California, Los AngelesDr. Nicholas C. Brecha, ChairRetinal ganglion cell (RGC) death has been attributed to aberrant calcium signaling in injury and disease. Calcium has a dual nature in mediating both homeostatic and apoptotic signaling pathways that modulate cell survival and cell death, respectively. The regulation of excessive calcium signaling through the inhibition of voltage-gated calcium channels (VGCCs) provides a potential strategy to reduce the loss of RGCs in injury and disease. My dissertation outlines the identification and contribution of the VGCCs, their modulation through the use of pharmacological blockers and the identification of an injury-resistant subtype of RGCs to provide a platform for future studies to investigate the expression and functional properties of VGCCs that may contribute to the superior ability to withstand injury. Calcium channel expression studies that utilized immunohistochemical techniques localized the L-, P/Q- and N-type VGCCs to the RGCs and the L-type VGCCs to the RGC axons. Weak immunostaining of the N-type VGCC was detected in the RGC axons. Likewise, calcium imaging studies investigating the functional contributions of the VGCCs provided evidence for the L-, P/Q-, N- and T-type VGCCs to the RGCs and the L-type VGCCs to the RGC axons. Patch clamp analysis further confirmed the presence of T-type VGCCs in RGCs. Lastly, the survival of RGCs and their axons that underwent optic nerve transection was investigated to identify a RGC type that is more resistant to injury than any other RGC type in the retina. Immunohistochemical analysis further confirmed the M1 RGC as the most resistant RGC type in the retina to injury
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Neuropeptide releasing amacrine cells modulate microcircuits in the inner retina
Get PDFAmacrine cells form the most diverse group of interneurons in the retina. There are at least 30 identified types, which are differentiated based on their stratification patterns, neurotransmitter content, and soma and dendritic field sizes. Despite knowing the morphology of each amacrine cell type, our understanding of the connectivity, intrinsic, and functional properties of a majority of the amacrine cell types remain unclear. This study aims to investigate the intrinsic properties of neuropeptide-expressing amacrine cells, as well as their role in modulating inner retinal microcircuits. These studies will focus on two neuropeptide-expressing amacrine cells examined are the somatostatin-expressing (SRIF) and vasoactive intestinal polypeptide-expressing (VIP) amacrine cells. Previous studies have shown SRIF and VIP amacrine cells play a role in regulating dopamine levels or modulating GABA signaling in the inner retina. In this study we tested how SRIF amacrine cells can modulate the cells that comprise the light adaptation network: dopamine-expressing (DA) amacrine cells and melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). In addition, we used a novel transgenic mouse line to map the intrinsic electrophysiological properties and synaptic partners of VIP amacrine cells.In order to address these questions about SRIF- and VIP-amacrine cells in the network of cells in the inner retina, I employed a combination of anatomical, pharmacological, and electrophysiological manipulations in multiple transgenic mouse lines. The 3D modeling generated from antibody-labeled whole mount retinas showed the relationship of the processes of SRIF- and DA-amacrine cells, as well as the processes between SRIF amacrine cells and melanopsin ipRGCs. Using pharmacology and whole patch clamp protocols I showed SRIF, acting through specific SRIF receptor subtypes (sst2A and sst4), effectively increases K+ currents, decreases Ca2+ currents, as well as regulate the spontaneous firing rate of both cell types. In addition, SRIF can directly inhibit the intrinsic light response of melanopsin ipRGCs.Using the VIP-tdTomato transgenic mouse line we detail the ion channel composition of VIP- amacrine cells, which include delayed inward rectifying K+ channels, verapamil-sensitive L-type Ca2+ channels, a hyperpolarizing activated K= channel (Ih), and TTX-sensitive Na+ channel currents. The recorded VIP amacrine cells showed varying combination of these ion channels, suggesting there may be multiple subtypes of VIP amacrine cells. Finally, using a puff protocol, we showed VIP amacrine cells receive inhibitory inputs mediated by GABA and glycine. In addition, they receive excitatory input from type 2 OFF- and type 6 ON-cone bipolar cells, likely through activation of an ionotropic glutamate receptor subtype, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
Heterogeneous functional organization of somatostatin- and dopamine-containing wide-field amacrine cells in mouse retina
Get PDFIn the retina, somatostatin (SRIF) is an inhibitory neuropeptide that influences multiple cell types, including bipolar, amacrine and ganglion cells. SRIF is reported to have multiple cellular actions including modulation of the release of dopamine (DA) from tyrosine hydroxylase (TH)-containing amacrine cells; however, the cellular basis of this interaction is unknown. Using immunohistochemistry I showed SRIF- and TH-containing wide-field amacrine cells co-stratify in the OFF sublamina of the inner plexiform layer (IPL) adjacent to the inner nuclear layer (INL). These processes form a dense network, which co-ramify and make numerous contacts along their processes and at varicosities. SRIF- and TH-immunoreactive (IR) cell bodies and processes also contain GABA and vesicular GABA transporter (VGAT) immunoreactivity, and express the GABAA α3 receptor subunit. TH-IR cells also express the SRIF receptor subtype 2A (sst2A) and SRIF-IR cells express the D1 receptor. Calcium imaging recordings of Fluo-4 labeled TH-red fluorescent protein (TH-RFP) processes exhibited a ~40% decrease in fluorescent intensity following 60 mM [K+] depolarization in the presence of SRIF (100nM-100 μM) and L054264 (1-10μM), a selective sst2A agonist. These findings suggest a reciprocal relationship between these two amacrine cell types mediated by both feedback and feed forward actions. SRIF amacrine cells act at TH-containing amacrine cells by a paracrine mechanism at sst2A, as well as directly at GABAA receptors. TH amacrine cells likely act at SRIF-containing amacrine cells at D1 and GABAA receptors. This retinal microcircuit defines a novel modulatory relationship for SRIF and demonstrates its broad influence on multiple visual processes
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
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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