40 research outputs found
Molecular Mechanisms of Fear Learning and Memory
No full textPavlovian fear conditioning is a particularly useful behavioral paradigm for exploring the molecular mechanisms of learning and memory because a well-defined response to a specific environmental stimulus is produced through associative learning processes. Synaptic plasticity in the lateral nucleus of the amygdala (LA) underlies this form of associative learning. Here, we summarize the molecular mechanisms that contribute to this synaptic plasticity in the context of auditory fear conditioning, the form of fear conditioning best understood at the molecular level. We discuss the neurotransmitter systems and signaling cascades that contribute to three phases of auditory fear conditioning: acquisition, consolidation, and reconsolidation. These studies suggest that multiple intracellular signaling pathways, including those triggered by activation of Hebbian processes and neuromodulatory receptors, interact to produce neural plasticity in the LA and behavioral fear conditioning. Collectively, this body of research illustrates the power of fear conditioning as a model system for characterizing the mechanisms of learning and memory in mammals and potentially for understanding fear-related disorders, such as PTSD and phobias
Stability of presynaptic vesicle pools and changes in synapse morphology in the amygdala following fear learning in adult rats
No full textSynapses lacking astrocyte appear in the amygdala during consolidation of pavlovian threat conditioning
No full text
Polyribosomes Redistribute from Dendritic Shafts into Spines with Enlarged Synapses during LTP in Developing Rat Hippocampal Slices
No full textAbstractThe presence of polyribosomes in dendritic spines suggests a potential involvement of local protein synthesis in the modification of synapses. Dendritic spine and synapse ultrastructure were compared after low-frequency control or tetanic stimulation in hippocampal slices from postnatal day (P)15 rats. The percentage of spines containing polyribosomes increased from 12% ± 4% after control stimulation to 39% ± 4% after tetanic stimulation, with a commensurate loss of polyribosomes from dendritic shafts at 2 hr posttetanus. Postsynaptic densities on spines containing polyribosomes were larger after tetanic stimulation. Local protein synthesis might therefore serve to stabilize stimulation-induced growth of the postsynaptic density. Furthermore, coincident polyribosomes and synapse enlargement might indicate spines that are expressing long-term potentiation induced by tetanic stimulation
Shifting patterns of polyribosome accumulation at synapses over the course of hippocampal long-term potentiation
No full textCYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation
No full textThe CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia. CYFIP1 plays a dual role in two apparently unrelated processes, inhibiting local protein synthesis and favoring actin remodeling. Here, we show that brain-derived neurotrophic factor (BDNF)-driven synaptic signaling releases CYFIP1 from the translational inhibitory complex, triggering translation of target mRNAs and shifting CYFIP1 into the WAVE regulatory complex. Active Rac1 alters the CYFIP1 conformation, as demonstrated by intramolecular FRET, and is key in changing the equilibrium of the two complexes. CYFIP1 thus orchestrates the two molecular cascades, protein translation and actin polymerization, each of which is necessary for correct spine morphology in neurons. The CYFIP1 interactome reveals many interactors associated with brain disorders, opening new perspectives to define regulatory pathways shared by neurological disabilities characterized by spine dysmorphogenesis
Evidências de validade de uma bateria informatizada para avaliação da personalidade adaptada ao desenho universal
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Filosofia e Ciências Humanas, Programa de Pós-Graduação em Psicologia, Florianópolis, 2013Este estudo teve como objetivo geral buscar evidências de validade da adaptação de um teste psicológico informatizado para avaliação da personalidade aos princípios do Desenho Universal. O teste foi adaptado para um formato fundamentado nos princípios do Desenho Universal e aplicado em pessoas com e sem deficiência visual. A presente pesquisa enquadra-se no âmbito dos estudos de busca por evidências de validade dos testes psicológicos. A busca por estas evidências é fundamental para avaliação das consequências das adaptações sobre possíveis interpretações dos resultados de testes, o qual é ainda um fenômeno pouco estudado. O estudo foi quantitativo com desdobramentos qualitativos e os instrumentos utilizados na pesquisa foram uma forma do teste adaptada aos princípios do Desenho Universal e um instrumento para que os participantes avaliassem quão bem o teste Informatizado para avaliação da personalidade adaptado atende aos princípios do Desenho Universal/Testagem Universal. Primeiramente, foram realizadas as adaptações do teste psicológico que avalia personalidade e o desenvolvimento do instrumento para avaliação do Desenho Universal. A amostra do estudo constou de 146 indivíduos com deficiência visual e 150 indivíduos sem deficiência. A parte qualitativa do estudo envolveu a avaliação do desempenho dos leitores de tela, as adaptações realizadas ao teste para torná-lo mais acessível e as análises dos resultados do instrumento para avaliação da aplicação da Testagem Universal. Já a parte quantitativa englobou o estudo das propriedades psicométricas do teste para avaliação da personalidade adaptado ao Desenho Universal, o estudo da função diferencial do item (DIF) e da função diferencial do teste (DTF), o estudo das diferenças de aptidão entre os grupos (impacto) e, por fim, o estudo de precisão. Os resultados obtidos sustentam a hipótese de que as medidas alcançadas com o teste adaptado podem ser utilizadas e interpretadas de uma forma semelhante para os deficientes visuais e para os indivíduos sem deficiência. Conclui-se, portanto, que a pesquisa relatada nesta dissertação deparou-se com evidências iniciais que atestam a validade do teste adaptado ao Desenho Universal The present study aims at understanding the process of meanings construction concerning depression from the perspective of psychologists´ practices in a city´s public mental health care system. This study has a qualitative approach and it was developed from the epistemological perspective of the Complex Thought, following the principles of the grounded theory. For this research, twenty-two psychologists working in the city mental health care system participated. The data collection began through a process of participant field observation, which enabled the understanding of the institutional context regarding the public policies of mental health care and work processes. The following stage was the application of the Knowledge on Depression Questionnaire (Questionário de Conhecimentos sobre Depressão) and the semi-structured interview. For the organization and integration of the set of data from the different instruments, there were established three main analytical dimensions, each one composed of categories, sub-categories and elements of analysis. The results show that the participants presented two meanings about conceptual understanding of depression: conceptualization of mental disorder, the prevailing meaning among the psychologists, or a symptom of an emotional conflict, which characterized a more psychological consideration of the phenomenon. Concerning the etiological understanding, the psychologists recognize the complexity of interaction of the multiple factors in the development for the depression, and how these factors must be observed in conducting the diagnosis process. They have also evinced that the diagnostic process must have an emphasis on the listening process of the subjectivity of the psychological demand in the context of the patient´s life history. Regarding the clinical management, the psychologists presented meanings that evidence a practice committed to a view of the patient as a singular individual, taking into account the social context and its importance when evaluating and discussing a therapeutic project in a multidisciplinary process. These meanings integrates the principles of the extended and shared clinical guiding concepts (clínica ampliada e compartilhada), based on a interdiciplinary and comprehensive understanding of the clinical process as, recommended by the Brazilian Department of Health (Ministério da Saúde, 2009). As to the context of the public mental health care system, psychologist perceive depression as the most prevalent mental disorder in Primary and secondary Care system
Theorizing and quantifying organizational and social factors in probabilistic risk assessment of complex systems
No full textOrganizational and social factors remain elusive and latent contributors to incidents and accidents in high-consequence industries, such as nuclear power, aviation, oil and gas, and healthcare. Probabilistic Risk Assessment (PRA) is a formal methodology for estimating risk emerging from the interactions of equipment failure and human error. This research is the product of a line of a collaborative study to theorize and quantify the explicit incorporation of organizational and social factors into PRA of complex technological systems, specifically for Nuclear Power Plants (NPPs) to; (a) make risk assessments more accurate, and (b) improve risk management and prevention by identifying and ranking critical organizational/social factors based on their influences on the technical system risk.
For NPPs, PRA can be used to generate three levels of risk information, including risk from reactor core damage (Level 1 PRA), the risk from loss of containment integrity (Level 2 PRA), and risk to the population and environment (Level 3 PRA). This dissertation is the product of multidisciplinary and collaborative PRA research activities, covering six journal manuscripts, and theorizes and quantifies organizational/social factors from two levels of analysis:
1. Meso-Level; meso-level organizational factors contribute to incidents or accidents in Level 1 PRA (e.g., Core Damage Frequency (CDF) in NPPs). Chapters 2 to 4 of the thesis cover the following contributions to the meso-level analysis:
a. Presents a discourse on the incorporation of organizational factors into PRA by summarizing key questions associated with the incorporation of organizational factors into PRA, framing the ongoing debates surrounding the topic, providing a categorical review of literature, and highlighting the directions of research required to reach a resolution for each question;
b. Expands the granularity of the Socio-Technical Risk Analysis (SoTeRiA) theoretical framework.
c. Advances the Integrated PRA (I-PRA) methodological framework to operationalize the SoTeRiA theoretical framework by developing the Data-Theoretic (DT) input module, which has two sub-modules: (1) DT-BASE, for developing detailed theory-based causal relationships in the Socio-Technical Risk Analysis (SoTeRiA) theoretical framework, equipped with a software-supported BASEline quantification utilizing information extracted from literature, industry reports, and regulatory standards, and (2) DT-SITE, conducting data analytics to refine and measure the causal factors of SoTeRiA based on system-specific historical event databases and using Bayesian analysis to update the baseline quantification. The methdology is applied using NPP database.
d. Applies DT-BASE to theorize and quantify a causal model of an NPP’s organizational “training system” and performs sensitivity analysis to identify critical factors. The computational platform of DT-BASE eases the execution of theory-building to expand theoretical details in SoTeRiA.The results indicate that among all the causal factors, “Program Design,” “Training Procedures/Facility,” and “Instructor Performance” are identified as the first, second, and third most important factors, respectively.
e. Applies DT-SITE, using the “training system” causal model from DT-BASE, to conduct text mining of Licensee Event Reports (LERs) from the U.S. nuclear power industry to generate the probability of “poor training quality.” Using the results of DT-SITE, the resulting probability of “poor training quality,” is estimated as 7.03E-07.
2. Macro-Level; macro-level social factors contribute to consequences of emergency response in Level 3 PRA (e.g., population radiological dose exposure). Chapters 5 and 6 of the thesis cover the following contributions to the macro-level analysis:
a. Develops a macro-level socio-technical risk analysis theoretical framework of factors influencing emergency response to a radiological hazard, considering onsite and offsite response organization performance, socio-technical infrastructure, multi-hazard interactions, and population protective action performance. The advanced theoretical framework contributes to the comprehensiveness of Level 3 PRA by considering a broader set of influencing factors and their multi-level interrelationships, providing opportunities for improved root cause analysis and development of radiological emergency response plans.
b. Develops an external integration between a radiological hazard and social vulnerability, a commonly used indicator in natural hazard research, and conducts risk importance measure analysis. The results reveal that the Center for Disease Control (CDC) Social Vulnerability Index (SVI) theme contributions to socio-technical risk can vary significantly by location.
c. Introduces an internally-integrated methodological framework for building and validating an HRA-based Population Departure Time Model (PDTM), and integrating it with the transportation evacuation model to generate model-based Evacuation Time Estimates (ETEs) and evacuation speed estimates as inputs to Level 3 PRA model. This integrated methodology makes an advancement toward the explicit incorporation of social factors into Level 3 through the explicit incorporation of social factors into departure time and evacuation speed estimations. The integrated methodology can help (i) create a more realistic estimation of risk from Level 3 PRA by contributing to a more realistic representation of population evacuation performance and (ii) provide the opportunity to conduct importance ranking of the social factors, influencing departure time and evacuation speed, with respect to their impacts on risk.
d. Applies the internally-integrated methodology for Level 3 PRA in a case study using results from the 2017 Sequoyah SOARCA study.
Lastly, to justify the ‘market value’ of PRA, and provide incentives for companies to make investments in PRA, for example, investing in the explicit incorporation of organizational/social factors, Chapter 7 of this dissertation analyzes the monetary value of PRA.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-05-01The student, Justin Pence, accepted the attached license on 2020-05-02 at 18:10.The student, Justin Pence, submitted this Dissertation for approval on 2020-05-02 at 18:15.This Dissertation was approved for publication on 2020-05-05 at 08:26.DSpace SAF Submission Ingestion Package generated from Vireo submission #15173 on 2020-08-25 at 17:42:38Made available in DSpace on 2020-08-27T00:50:17Z (GMT). No. of bitstreams: 4
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