Mammalian neurons exhibit extreme sensitivity to oxygen deprivation and undergo rapid and irreversible degeneration when oxygen supply is curtailed. Though several neuroprotective pathways are activated during oxygen deprivation, their analyses are masked by the complex series of pathological events which are triggered simultaneously. Such events can be analyzed in the anoxia tolerant fresh water turtle, which can inherently survive the conditions of oxygen deprivation and post-anoxic reoxygenation without brain damage. It is likely in such a model that modulation of a particular molecular pathway is adaptive rather than pathological. The major objective behind this study was to analyze the intracellular signaling pathways mediating the protective effects of adenosine, a potential neuromodulator, and its effect on cell survival by influencing the key prosurvival proteins that prevent apoptosis. In vivo and in vitro studies have shown that adenosine acts as a neuroprotective metabolite and its action can be duplicated or abrogated using specific agonist and antagonists. Stimulating the adenosine receptors using selective A1 receptor agonist N6-cyclopentyladenosine (CPA) activated the presumed prosurvival ERK and P13-K/AKT cascade promoting cell survival, and suppression of the receptor using the selective antagonist DPCPX (8- cyclopentyl-1,3-dipropylxanthine) activated the prodeath JNK and P38 pathways. The complex regulation of the MAPK's/AKT signaling cascades was also analyzed using their specific inhibitors. The inhibiton of the ERK and AKT pathway increased cell death, indicating a prosurvival role, whereas inhibiton of the JNK and p38 pathway increased cell survival in this model. In vitro studies have also shown a high Bcl-2/BAX ratio during anoxia and reoxygenation, indicating a strong resistance to cell death via apoptosis. / Silencing of the anti-apoptotic Bcl-2 gene using specific siRNA upregulated levels of prodeath BAX, thus altering the Bcl-2/BAX ratio and elevating cleaved Caspase-3 levels leading to increased cell death. Another promising neuroprotective target which we analyzed was Neuroglobin, which was induced during oxygen crisis and silencing this gene indicated that its plays a major role in modulation of ROS. This study strongly emphasizes the advantages of an alternate animal model in elucidating neuroprotective mechanisms and revealing novel therapeutic targets which could eventually help clinicians to design new stroke therapies based on naturally tolerant organisms. / by Gauri Nayak. / Thesis (Ph.D.)--Florida Atlantic University, 2009. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2009. Mode of access: World Wide Web.

Neuronal cell adhesion molecules of L1 family play a critical role in proper nervous system development. Various mutations on human L1-CAM that lead to severe neurodevelopmental disorders like retardation, spasticity etc. termed under L1 syndrome. The vertebrr their roles in axon pathfinding, neurite extension and cell migration, howeverate L1CAM and its homolog in Drosophila, neuroglian (nrg) have been well studied fo, much less is known about the mechanisms by which they fine tune synaptic connectivity to control the development and maintenance of synaptic connections within neuronal circuits. Here we characterized the essential role of nrg in regulating synaptic structure and function in vivo in a well characterized Drosophila central synapse model neuron, the Giant Fiber (GF) system. Previous studies from our lab revealed that the phosphorylation status of the tyrosine in the Ankyrin binding FIGQY motif in the intracellular domain of Nrg iscrucial for synapse formation of the GF to Tergo-Trochanteral Motor neuron (TTMn) synapse in the GF circuit. The present work provided us with novel insights into the role of Nrg-Ank interaction in regulating Nrg function during synapse formation and maintenance. By utilizing a sophisticated Pacman based genomic rescue strategy we have shown that dynamic regulation of the Neuroglian–Ankyrin interaction is required to coordinate transsynaptic development in the GF–TTMn synapse. In contrast, the strength of Ankyrin binding directly controls the balance between synapse formation and maintenance at the NMJ. Human L1 pathological mutations affect different biological processes distinctively and thus their proper characterization in vivo is essential to understand L1CAM function. By utilizing nrg14;P[nrg180ΔFIGQY] mutants that have exclusive synaptic defects and the previously characterized nrg849 allele that affected both GF guidance and synaptic function, we were able to analyze pathological L1CAM missense mutations with respect to their effects on guidance and synapse formation in vivo. We found that the human pathological H210Q, R184Q and Y1070C, but not the E309K and L120V L1CAM mutations affect outside-in signaling via the FIGQY Ankyrin binding domain which is required for synapse formation and not for axon guidance while L1CAM homophilic binding and signaling via the ERM motif is essential for axon guidance in Drosophila. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

A circuitaria neuro-anatômica envolvida com a organização de respostas de medo inclui muitos sítios subcorticais diferentes, dois dos quais são a região dorsal da matéria cinzenta periaquedutal (dPAG) e as camadas intermediárias e profundas do colículo superior (i/dlSC). Este estudo investigou como as células destas duas regiões mudam de atividade em um rato que foi colocado diante de seu predador, o gato, comparado com outras situações onde o risco menor. 11 ratos wistar machos passaram por cirurgia para implantação de um microdriver contendo 8 tetrodos, que detectou 39 células na dPAG de 7 ratos e 44 células nas i/dlSC de 4 ratos. A atividade das células foi registrada em uma condição de base e em quatro condições experimentais distintas: o rato confinado, o rato diante de uma novidade, diante de um predador e diante do contexto predatório. Os dados coletados foram analisados por scripts de MATLAB e cada célula foi classificada para sua responsividade às condições experimentais, à mudança do comportamento do rato, à velocidade e à posição do rato no aparato. Na dPAG as células se mostraram mais responsivas a condição do gato do que as demais condições experimentais, tanto em número de células como em aumento de atividade celular. Uma quantidade menor de células mostrou-se responsiva a mudanças de comportamento, particularmente os comportamentos de defesa. Nas i/dlSC as células também se mostraram mais responsivas para o gato, seguido do contexto, em ambos os casos com diminuição de atividade celular, que foi mais intensa no gato. Uma quantidade menor de células pareceu responder de forma similar para as diferentes mudanças comportamentais. Interpretamos esses dados propondo que a dPAG possui uma função sinalizadora de medo, fortemente ativada durante o gato, e que as i/dlSC são inibidas diante do gato a fim de evitar a captação de estímulos irrelevantes para lidar com a situação de risco. / The neuroanatomical circuitry involved with the organization of fear responses includes a great number of subcortical sites, two of which are the dorsal periaqueductal gray (dPAG) and the intermediate and deep layers of the superior colliculus (i/dlSC). This study investigated how the cellular activity in these regions changed in a rat that was exposed to one of its predators, a cat, when compared with lower risk situations. 11 male wistar rats underwent surgery to implant a microdriver containing 8 tetrodes, which detected 39 cells in the dPAG of 7 rats and 44 cells in the i/dlSC of 4 rats. Cell activity was registered in a basal condition and then again in for experimental conditions: the rat confined in a smaller space, the rat facing a novel stimulus, the rat facing a cat and the rat facing the predatory context. Collected data was analyzed using MATLAB and each cell was classified according to its responsivity to the experimental conditions, to the rats switches in behavior, to the rats speed and position in the experimental apparatus. In the dPAG, cells were shown to be more responsive to the cat condition over the other conditions, both in terms of number of responsive cells and intensity of increase in firing activity. A smaller number of cells were responsive to behavior switching, being especially sensitive to the initiation of defensive behaviors. In the i/dlSC, cells were more responsive to the cat, followed by the predatory context, in both cases with a general reduction of cellular activity that was more intensive for the cat. A smaller number of cells was responsive in similar ways for behavior switching across experimental conditions. We interpret this data by proposing that the dPAG acts signaling a state of fear, particularly during a high risk situation, and the i/dlSC are inhibited during riskier situations so as to block irrelevant environmental stimuli.

Esta é uma investigação sobre a formação do arquiteto em sua dimensão sensível. A visão persistente de que ser artista é uma condição inata de alguns seres humanos tem gerado dificuldades na ação de criar, entre os aprendizes de arquitetura, à revelia das descobertas da Ciência sobre as capacidades cerebrais do ser humano, descobertas que interferem nas reflexões sobre como acontece o conhecimento. Ainda dificulta essa formação, um mundo atual consumista e negativamente pragmático que interfere na missão formadora da instituição escola de arquitetura, querendo forçá-la a ser mero curso profissionalizante. Esse panorama apresenta uma estrutura de formação sem a condição de poder alcançar a sensibilidade do aprendiz para fazê-lo perceber, intuir, criar espaços com sua dimensão que supera a função de abrigo das atividades humanas: sua condição de Arte. Este é o motivo desta Tese: propor uma modificação na fisionomia das estruturas vigentes de formação do arquiteto para que ela possa ser mais estimuladora da sensibilidade de seus aprendizes. / This is a research on architect formation in its dimension of Art. The predominant and persistent view that to be an artist is an innate condition of some human beings has been producing difficulties in the action of creation, among the apprentices of architecture, which ignore the science discoveries about the human beings brains. Another difficulty to this formation is the present consumer and pragmatic world which interferes on the formative mission of the school of architecture institution, pretending enforced it to be a mere professional course. This scene presents a formation structure without a condition that could allow to reach the sensibility of the apprentice in order to make him perceive, feel, create spaces with his own dimensions which overcome the function of sheltering human activities: its Art dimension. This is the leitmotiv of this thesis: to propose another physiognomy to the present structure for the architect formation as a way to make it more stimulating to the sensibility of its apprentices.

The neurophysiological pathways associated with beat-to-beat regulation of mean arterial pressure are well known. Less known are the control dynamics associated with short term maintained of arterial blood pressure about a homeostatic set point.The baroreflex (BRx), the most rapid and robust of neural reflexes within the autonomic nervous system, is a negative feedback controller that monitors and regulates heart rate and blood pressure. By leveraging the parasympathetic and sympathetic divisions of the autonomic nervous system, the BRx can change blood pressure within a single heart beat. To better understand these controller dynamics, a classic BRx reflexogenic experimental preparation was carried out. This thesis reconfirmed previous observations of an electrically-evoked sexually-dimorphic peak depressor response in the BRx of Sprague-Dawley rats and verified that these functional reflexogenic differences carry over to sustained electrical paradigms. Further, it uncovered interesting recovery dynamics in both blood pressure and heart rate. The rat aortic depressor nerve was used as an experimental target for electrical activation of the parasympathetic-mediated reduction in mean arterial pressure. The duration, frequency, and patterning of stimulation were explored, with emphasis on differences between sexes. By measuring the normalized percent decrease in mean arterial pressure as well as the differences in beats per minute during rest and during stimulation,the null hypothesis was rejected.<br>

Finding novel compounds that affect neuronal or muscular function is of great interest, as they can serve as potential pharmacological agents for a variety of neurological disorders. For instance, conopeptides have been developed into powerful drugs like the painkiller PrialtTM. Most conopeptides, however, have yet to be characterized, revealing the need for a rapid and straightforward screening method. We have designed a novel bioassay, which allows for unbiased screening of biological activity of compounds in vivo against numerous molecular targets on a wide variety of neurons and muscles in a rapid and straightforward manner. For this, we paired nanoinjection of compounds with electrophysiological recordings from the Giant Fiber System of Drosophila melanogaster, which mediates the escape response of the fly. / by Monica Mejia. / Thesis (Ph.D.)--Florida Atlantic University, 2013. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

Fidgeting and otherwise constant movements in individuals can be beneficial in those who suffer from Attention Deficit/Hyperactivity Disorder or Generalized Anxiety Disorder as well as others. However this constant movement can also be a distraction to others as well as protrude an air of no self confidence. It is the drawbacks from these actions that we wish to address. By developing an intelligent system that can detect these motions and alert the user, it will allow the wearer of the device to self correct. It is in this self control that one may exhibit more confidence or simply reduce the level of irritation experienced by those in the immediate vicinity. We have designed and built a low cost, mobile, lightweight, untethered, wearable prototype device. It will detect these actions and deliver user selectable biofeedback through a light emitting diode, buzzer, vibromotor or an electric shock to allow for self control. / by Scott A. Barnard. / Thesis (M.S.C.S.)--Florida Atlantic University, 2009. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2009. Mode of access: World Wide Web.

Cardiac ischemia, stroke and some neurodegenerative disorders are all characterized by cell damage and death due to low oxygen levels. Comparative studies show that anoxia tolerant model systems present a unique opportunity to study "survival" instead of death in the complete absence of oxygen. The freshwater turtle (Trachemys scripta elegans) is unique in its ability to survive total oxygen deprivation for hours to days, as well as reoxygenation insult after anoxia. The broad objective of this study is to understand the modulation of key molecular mechanisms involving stress proteins and VEGF that offer neuroprotection and enhance cell survival in the freshwater turtle through anoxia and reoxygenation. In vivo analyses have shown that anoxia induced stress proteins (Hsp72, Hsp60, Grp94, Hsp60, Hsp27, HO-1); modest changes in the Bcl2/Bax ratio and no change in cleaved caspase-3 expression suggesting resistance to neuronal damage. These results were corroborated with immunohistochemical evidence indicating no damage in turtle brain when subjected to the stress of anoxia and A/R. To understand the functional role of Hsp72, siRNA against Hsp72 was utilized to knockdown Hsp72 in vitro (neuronally enriched primary cell cultures established from the turtle). Knockdown cultures were characterized by increased cell death associated with elevated ROS levels. Silencing of Hsp72 knocks down the expression of Bcl2 and increases the expression of Bax, thereby decreasing the Bcl2/Bax ratio. However, there was no increase in cytosolic Cytochrome c or the expression levels of cleaved Caspase-3. Significant increase in AIF was observed in the knockdown cultures that increase through anoxia and reoxygenation, suggesting a caspase independent pathway of cell death. / Expression of the master regulator of hypoxia, HIF1 alpha and its target gene, VEGF, were analyzed at the mRNA and protein levels. The results showed no significant increase in HIF-1 alpha levels but anoxia VE GF The levels of stress proteins and VEGF returned to control levels during reoxygenation suggesting robust ROS protection mechanisms through reoxygenation. The present study thereby emphasizes Trachemys scripta as an advantageous model to examine anoxia and reoxygenation survival without major damage to the brain due to it's modulation of molecular mechanisms. / by Shailaja Kesaraju. / Thesis (Ph.D.)--Florida Atlantic University, 2008 / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2008. Mode of access: World Wide Web.

This study investigated electroencephalographic differences related to cue (central left- or right-directed arrows) in a covert endogenous visual spatial attention task patterned after that of Hopf and Mangun (2000). This was done with the intent of defining the timing of components in relation to cognitive processes within the cue-target interval. Multiple techniques were employed to do this. Event-related potentials (ERPs) were examined using Independent Component Analysis. This revealed a significant N1, between 100:200 ms post-cue, greater contralateral to the cue. Difference wave ERPs, left minus right cue-locked data, divulged significant early directing attention negativity (EDAN) at 200:400 ms post-cue in the right posterior which reversed polarity in the left posterior. Temporal spectral evolution (TSE) analysis of the alpha band revealed three stages, (1) high bilateral alpha precue to 120 ms post-cue, (2) an event related desynchronization (ERD) from approximately 120 ms: 500 ms post-cue, and (3) an event related synchronization (ERS) rebound, 500: 900 ms post-cue, where alpha amplitude, a measure of activity, was highest contralateral to the ignored hemifield and lower contralateral to the attended hemifield. Using a combination of all of these components and scientific literature in this field, it is possible to plot out the time course of the cognitive events and their neural correlates. / by Edward Justin Modestino. / Vita. / Thesis (Ph.D.)--Florida Atlantic University, 2009. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2009. Mode of access: World Wide Web.

Body dissatisfaction (BD) is a condition derived from negative thoughts and feelings about one's body and is a core symptom of the eating disorder anorexia nervosa (AN). Beingdissatisfied with one’s body is highly present in women and to some extent men. This might be a result of a skewed ideal in combination with social influences. In recent year, research on neurobiological risk factors as well as neuroscientific and cognitive mappings of AN and BD have gained traction, particularly when it comes to studies using neuroimaging- techniques and cognitive tests. Studies have identified brain regions (insular cortex, anterior cingulate cortex, parietal cortex, amygdala, dorsolateral and orbitofrontal areas of the prefrontal cortex) associated with the processing of body shape as well as dysfunctional processing of self-image and body satisfaction. Structural imaging studies of AN patients using CT and MRI have, in many cases, found reduced cerebral volume, increased spinal fluid (CSF) and enlarged ventricles. Usually, food and water restriction has been seen as the cause, and structural deficits in AN patients have shown to improve with weight gain after long-term recovery.