Modulation of GABAergic signaling in retinal amacrine cells

The intricate circuitry formed by amacrine cells in the inner plexiform layer (IPL) of the retina suggests that these interneurons play a major role in shaping the visual message. The majority of amacrine cells in the vertebrate retina are GABAergic. Thus, elucidating how GABAergic signaling is modulated in the IPL is critical in order to understand how the visual message is processed in the retina. The results presented here suggest that GABAergic signaling between amacrine cells can be modulated by the activation of metabotropic glutamate receptor 5 (mGluR5) or by the production of the second messenger, nitric oxide (NO). A novel mGluR5 splice variant was isolated from the chicken retina with a truncated carboxy-terminal tail. Whole cell electrophysiological experiments indicated that activation of mGluR5 enhances GABA-gated currents recorded from cultured chick amacrine cells. This mGluR5-dependent enhancement occurred through the inositol 1,4,5-trisphosphate pathway and was dependent upon the release of Ca2+ from internal stores. The Ca2+-dependent protein kinase (PKC) was also required for the mGluR5-dependent enhancement as indicated by 1) enhancement of GABA-gated currents by PKC activators, 2) occlusion of the mGluR5-dependent enhancement by these activators, and 3) reduction of the mGluR5-dependent enhancement by a PKC inhibitor. The mGluR5-dependent enhancement of synaptic currents was nearly twice that observed for whole cell GABA-gated currents, suggesting that the receptors and signaling molecules are targeted to GABAergic synapses. NO also modulated GABAergic transmission between amacrine cells, but through two different pathways. Lower concentrations of NO released from NO donors enhanced GABA-gated currents by affecting the function of the GABAA receptors through a soluble guanylate cyclase-independent pathway. Higher concentrations of NO (NO-bubbled solutions) increased the intracellular Cl- concentration through an uncharacterized and potentially novel mechanism that possibly involves Cl- cotransporters. The NO-induced influx of Cl- shifts the Cl- equilibrium potential (ECl-) to more positive values. Furthermore, the NO-induced shift in ECl- allows GABA to depolarize the membrane potential, indicating that NO can convert an inhibitory GABAergic synapse to an excitatory synapse

San Antonio Museum of Art: Addressing the Needs of Cultural Consumers in the 21st Century

In January of 2012, I began an internship with the San Antonio Museum of Art. At the time, the Education Department was engrossed in an audience research study, designed to strengthen the Museum’s understanding of its constituents. This study was my entry-point into the organization and where all my efforts were focused over the course of my internship. This paper includes: an organizational summary; an account of my internship experiences; a SWOT analysis; a review of industry best practices; and recommendations based on observations acquired over the course of my internship

San Antonio Museum of Art: Addressing the Needs of Cultural Consumers in the 21st Century

In January of 2012, I began an internship with the San Antonio Museum of Art. At the time, the Education Department was engrossed in an audience research study, designed to strengthen the Museum’s understanding of its constituents. This study was my entry-point into the organization and where all my efforts were focused over the course of my internship. This paper includes: an organizational summary; an account of my internship experiences; a SWOT analysis; a review of industry best practices; and recommendations based on observations acquired over the course of my internship

Applications of Expanded WRAP Modeling Capabilities to the Brazos WAM

The Water Rights Analysis Package (WRAP) is routinely applied in the Texas Commission on Environmental Quality (TCEQ) Water Availability Modeling (WAM) System. However, the Brazos River Basin studies documented by this report represent inaugural applications of the following new WRAP modeling capabilities: (1) conditional reliability modeling to determine short-term storage and flow frequencies and supply reliabilities conditioned on preceding reservoir storage contents; (2) capabilities added to allow simulations to be performed with daily time steps; and (3) simulation of reservoir operations for flood control. The Brazos WAM studies presented in this report provide a data and experience base for evaluating, demonstrating, and developing guidance for applying the new WRAP modeling capabilities. The studies also provide a better understanding of water management in the Brazos River Basin

Nitric oxide transiently converts synaptic inhibition to excitation in retinal amacrine cells

Nitric oxide (NO) is generated by multiple cell types in the vertebrate retina, including amacrine cells. We investigate the role of NO in the modulation of synaptic function using a culture system containing identified retinal amacrine cells. We find that moderate concentrations of NO alter GABAA receptor function to produce an enhancement of the GABA-gated current. Higher concentrations of NO also enhance GABA-gated currents, but this enhancement is primarily due to a substantial positive shift in the reversal potential of the current. Several pieces of evidence, including a similar effect on glycine-gated currents, indicate that the positive shift is due to an increase in cytosolic Cl-. This change in the chloride distribution is especially significant because it can invert the sign of GABA- and glycine-gated voltage responses. Furthermore, current- and voltage-clamp recordings from synaptic pairs of GABAergic amacrine cells demonstrate that NO transiently converts signaling at GABAergic synapses from inhibition to excitation. Persistence of the NO-induced shift in ECl- in the absence of extracellular Cl- indicates that the increase in cytosolic Cl- is due to release of Cl- from an internal store. An NO-dependent release of Cl- from an internal store is also demonstrated for rat hippocampal neurons indicating that this mechanism is not restricted to the avian retina. Thus signaling in the CNS can be fundamentally altered by an NO-dependent mobilization of an internal Cl- store. Copyright © 2006 The American Physiological Society

Modulation of synaptic function in retinal amacrine cells

Amacrine cells are interneurons that have diverse functions in retinal signal processing. In order to study signaling and modulation in retinal amacrine cells, we employ a simplified culture system containing identifiable GABAergic amacrine cells. Immunocytochemistry experiments indicate that GABAergic amacrine cells express metabotropic glutamate receptor 5 (mGluR5), a group I mGluR usually linked to the IP3 signaling pathway. Ca2+ imaging experiments using an mGluR5-specific agonist indicate that these receptors are functional and when activated, can stimulate temporally diverse Ca2+ elevations. To begin to establish the role of these receptors in modulating amacrine cell function, we have used electrophysiological methods to ask whether ion channels are the targets of mGluR5-dependent modulation. Here we discuss our results indicating that activation of mGluR5 leads to enhancement of currents through GABAA receptors. This enhancement is dependent upon elevations in cytosolic Ca2+ and activation of protein kinase C (PKC). To explore the consequences of Ca2+ elevations in another context, we have used nitric oxide (NO) donors to mimic the effects of activating the Ca2+-dependent synthetic enzyme for NO, neuronal nitric oxide synthase. We find that exposure to NO donors also enhances the amplitude of currents through GABAA receptors. Together, these results indicate that glutamate from presynaptic bipolar cells has the potential to work through multiple mechanisms to regulate the function of amacrine-to-amacrine cell GABAergic synapses

Setting the standard: Perceptions and implementations of standards for mathematics teacher preparation programs

The development and use of standards have become a key aspect of education. Significant research has been conducted to understand the perceptions and implementations of standards in PK-12 school settings. There exists significantly less research focused on the understanding of standards for teacher preparation, especially within the field of mathematics teacher preparation. In the field of mathematics teacher preparation, multiple standards documents are available to inform practice. Among these include the standards used for accreditation purposes produced by the National Council of Teachers of Mathematics (NCTM) in partnership with the Council for the Accreditation of Educator Preparation (CAEP), the Standards for Preparing Teachers of Mathematics produced by the Association of Mathematics Teacher Educators (AMTE), and the Mathematical Education of Teachers (MET) documents produced by the Conference Board of the Mathematical Sciences (CBMS). While these represent the most well-known standards for mathematics teacher educators, other standards such as standards for PK-12 teachers including the Common Core State Standards are also related to the work of mathematics teacher preparation. In this complicated space of multiple standards from multiple perspectives, it is necessary to better understand the influence of these standards with mathematics teacher educators by better understanding how they are perceived and implemented. In this case study, eight mathematics teacher educators shared how they perceived and implemented standards within their programs. The findings of this research included navigating standards, standards as tools of accountability and compliance, the intersection of standards and curriculum, collaborating for enacting the standards, and care for students and their experiences. In these findings, participants shared how standards related to ideas of best practice. These ideas about standards being drawn from ideas of best practice are related to issues of compliance in accreditation as well as an indirect correlation with curriculum choices in program development and maintenance. In practice, this work was not done in isolation, but required interdepartmental collaboration as well as consideration for the needs of individual students. Keywords: Teacher Education, Standards, Mathematics, Accreditatio

Trim14 Is a Key Regulator of the Type I Interferon Response during Mycobacterium tuberculosis Infection

TRIM (tripartite motif) family proteins are distinguished as important players in the innate immune response to infection. TRIM14 has been heavily implicated in anti-viral innate immune signaling through various protein-protein interactions. However, TRIM14’s role during bacterial infection remains unclear. Here, I demonstrate that TRIM14 is a crucial negative regulator of type I interferon and interferon stimulated gene (ISG) expression during infection with Mycobacterium tuberculosis, a potent activator of cytosolic DNA sensing pathways. My data shows that TRIM14 directly interacts with the DNA sensing kinase TBK1 and that loss of TRIM14 leads to dramatic hyper-induction of IFN and ISGs in response to cytosolic nucleic acid agonists, including M. tuberculosis. Consistent with this phenotype, I report that loss of TRIM14 promotes phosphorylation of STAT3 at S754, leading to downregulation of negative regulators of ISG expression including SOCS3. Furthermore, in investigating ways in which TRIM14 could be regulated we discovered an isoform of TRIM14 that is upregulated upon M. tuberculosis infection. In addition, TRIM14 is differentially ubiquitinated and phosphorylated upon bacterial infection. I propose here that TRIM14 manipulates the host innate immune response against different pathogens at several distinct regulatory steps. Ultimately, TRIM14 activity may prove to be a good therapeutic target as limiting its activity could promote clearance of Mycobacterium tuberculosis infection