Thesis (M. S.)--Psychology, Georgia Institute of Technology, 2009. / Committee Chair: Dr. Paul Corballis, Ph.D.; Committee Member: Dr. Daniel Spieler, Ph.D.; Committee Member: Dr. Eric Schumacher, Ph.D.; Committee Member: Dr. Krish Sathian, M.D., Ph.D.; Committee Member: Dr. Randall Engle, Ph.D.

Thesis (M.Sc.) - Carleton University, 2007. / Includes bibliographical references (p. 78-87). Also available in electronic format on the Internet.

Thesis (Ph.D.)--Brandeis University, 2010. / "UMI:3390479." MICROFILM COPY ALSO AVAILABLE IN THE UNIVERSITY ARCHIVES. Includes bibliographical references.

Thesis (Ph.D.)--University of California, San Francisco, 2004. / Includes bibliographical references. Also available online.

As epilepsias acometem entre 1-2% da população mundial. De um modo geral, de todas as epilepsias quase um terço deste total de pacientes apresenta a síndrome epiléptica conhecida como Epilepsia de Lobo Temporal (ELT), a qual se instala geralmente após um insulto inicial ou em decorrência de outras patologias como, por exemplo, trauma ou tumor, e parece ser decorrente de anormalidades intrínsecas do lobo temporal tais como, amígdala, hipocampo e córtex piriforme. Depois de um período de latência variado, promove o surgimento de crises convulsivas. Dentre os pacientes que apresentam ELT, cerca de 20 a 30% deles apresentam resistência ao tratamento farmacológico. Para melhor estudar os processos plásticos envolvidos no processo de epileptogênese ocorridos após a instalação do insulto inicial que levam ao aparecimento de crises recorrentes espontâneas, ratos Wistar foram eletricamente estimulados na amígdala para indução de Status Epilepticus (SE). Foram feitas histoquímicas e immunohistoquímica para marcar neurônios ativados (c-Fos+), novos neurônios (Doublecortin DCX+) e em degeneração (FluoroJade C - FJC+) após as crises. Após a indução do SE observamos que quanto mais graves as crises, maior o número de áreas ativadas (c-Fos+) e maior número de neurônios em degeneração (FJC+). Além disso, não houve associação direta entre as áreas cerebrais ativadas e grau de neurodegeneração, nem associação entre gravidade do SE e intensidade de neurogênese (DCX). A segunda fase deste projeto, executada na University of Cincinnati, refere-se ao estudo do impacto do SE, induzido por pilocarpina (PILO) sistêmica, sobre a neurogênese hipocampal. Utilizando a injeção de BrdU, para marcar o dia do nascimento de novos neurônios granulares, em camundongos Thy1-GFP foram submetidos ao SE por PILO. Foram analisadas a plasticidade dendrítica de neurônios granulares em fase de maturação (imaturas, 1 semana) e maduras (8 semanas). As células imaturas sofreram drásticas modificações na sua morfologia e na densidade dendrítica. Por outro lado, as células maturas não sofreram alterações morfológicas na árvore dendrítica, mas apresentaram uma intensa redução na densidade dos espinhos dendríticos, mostrando assim que as células imaturas estão mais suceptíveis ao impacto das crises epilépticas. / The epilepsies affect between 1-2% of the world. In general, all epilepsies almost a third of total patients had an epilepsy syndrome known as temporal lobe epilepsy (TLE), which usually settles after the initial insult or due to other pathologies such as, for example, trauma or tumor, and seems to be due to intrinsic abnormalities such as temporal lobe, amygdala, hippocampus and piriform cortex. After latency period varied, promotes the emergence of seizures. Among the patients with TLE, about 20 to 30% of them are resistant to pharmacological treatment. To better study the processes involved in plastic epileptogenesis occurred after the installation of the initial insult leading to the appearance of spontaneous recurrent seizures, rats were electrically stimulated in the amygdala to induce status epilepticus (SE). Histochemical and immunohistochemistry were done to mark neurons activated (c-Fos +), newborn neurons (Doublecortin - DCX+) and degenerating (FluoroJade C - FJC+) after the crisis. After SE induction observed that the more serious crises, the greater the number of activated areas (c-Fos+) and greater number of degenerating neurons (FJC+). In addition, there was no direct association between the brain areas activated and the degree of neurodegeneration, or association between the severity and intensity of the SE of neurogenesis (DCX+). The second phase of this project, performed at the University of Cincinnati, refers to study the impact of SE induced by pilocarpine (Pilo) system on hippocampal neurogenesis. Using the injection of BrdU, to label the daybirth of new granule neurons in Thy1-GFP mice subjected to SE. We analyzed the dendritic plasticity of granule neurons undergoing maturation (immature, 1 week) and mature (8 weeks). The immature cells have undergone drastic changes in their dendritic morphology and density. On the other hand, the mature cells did not undergo morphological changes in dendritic tree but showed a marked decrease in the density of dendritic spines, thus showing that immature cells are more susceptible to the impact of epileptic seizures.

The consequences of myo-cardial ischemia are examined from the standpoint of the neural control system of the heart, a hierarchy of three neuronal centers residing in central command, intrathoracic ganglia, and intrinsic cardiac ganglia. The basis of the investigation is the premise that while this hierarchical control system has evolved to deal with "normal" physiological circumstances, its response in the event of myocardial ischemia is unpredictable because the singular circumstances of this event are as yet not part of its evolutionary repertoire. The results indicate that the harmonious relationship between the three levels of control breaks down, because of a conflict between the priorities that they have evolved to deal with. Essentially, while the main priority in central command is blood demand, the priority at the intrathoracic and cardiac levels is heart rate. As a result of this breakdown, heart rate becomes less predictable and therefore less reliable as a diagnostic guide as to the traumatic state of the heart, which it is commonly used as such following an ischemic event. On the basis of these results it is proposed that under the singular conditions of myocardial ischemia a determination of neural control indexes in addition to cardiovascular indexes has the potential of enhancing clinical outcome.

A model is proposed in which the relationship between individual neurons within a neural network is dynamically changing to the effect of providing a measure of "plasticity" in the control of heart rate. The neural network on which the model is based consists of three populations of neurons residing in the central nervous system, the intrathoracic extracardiac nervous system, and the intrinsic cardiac nervous system. This hierarchy of neural centers is used to challenge the classical view that the control of heart rate, a key clinical index, resides entirely in central neuronal command (spinal cord, medulla oblongata, and higher centers). Our results indicate that dynamic networking allows for the possibility of an interplay among the three populations of neurons to the effect of altering the order of control of heart rate among them. This interplay among the three levels of control allows for different neural pathways for the control of heart rate to emerge under different blood flow demands or disease conditions and, as such, it has significant clinical implications because current understanding and treatment of heart rate anomalies are based largely on a single level of control and on neurons acting in unison as a single entity rather than individually within a (plastically) interconnected network.

The consequences of myo-cardial ischemia are examined from the standpoint of the neural control system of the heart, a hierarchy of three neuronal centers residing in central command, intrathoracic ganglia, and intrinsic cardiac ganglia. The basis of the investigation is the premise that while this hierarchical control system has evolved to deal with "normal" physiological circumstances, its response in the event of myocardial ischemia is unpredictable because the singular circumstances of this event are as yet not part of its evolutionary repertoire. The results indicate that the harmonious relationship between the three levels of control breaks down, because of a conflict between the priorities that they have evolved to deal with. Essentially, while the main priority in central command is blood demand, the priority at the intrathoracic and cardiac levels is heart rate. As a result of this breakdown, heart rate becomes less predictable and therefore less reliable as a diagnostic guide as to the traumatic state of the heart, which it is commonly used as such following an ischemic event. On the basis of these results it is proposed that under the singular conditions of myocardial ischemia a determination of neural control indexes in addition to cardiovascular indexes has the potential of enhancing clinical outcome.

A model is proposed in which the relationship between individual neurons within a neural network is dynamically changing to the effect of providing a measure of "plasticity" in the control of heart rate. The neural network on which the model is based consists of three populations of neurons residing in the central nervous system, the intrathoracic extracardiac nervous system, and the intrinsic cardiac nervous system. This hierarchy of neural centers is used to challenge the classical view that the control of heart rate, a key clinical index, resides entirely in central neuronal command (spinal cord, medulla oblongata, and higher centers). Our results indicate that dynamic networking allows for the possibility of an interplay among the three populations of neurons to the effect of altering the order of control of heart rate among them. This interplay among the three levels of control allows for different neural pathways for the control of heart rate to emerge under different blood flow demands or disease conditions and, as such, it has significant clinical implications because current understanding and treatment of heart rate anomalies are based largely on a single level of control and on neurons acting in unison as a single entity rather than individually within a (plastically) interconnected network.

Performance motor errors trigger animals’ adaptive learning behaviors to improve the accuracy and efficiency of the movement. The cerebellum is one of the key brain centers for encoding motor performance and motor learning. Climbing fibers relay information related to motor errors to the cerebellar cortex, evoking elevation of intracellular Ca2+ signals at Purkinje cell dendrites and inducing plasticity at coactive parallel fiber synapses, ultimately recalibrating sensorimotor associations to alter behavior. Molecular layer interneurons (MLIs) inhibit Purkinje cells to modulate dendritic excitability and action potential output. How MLIs contribute to the regulation and encoding of climbing fiber-evoked adaptive movements remains poorly understood. In this dissertation, I used genetic tools to manipulate the activity of MLIs while monitoring Purkinje cell dendritic activity during a cerebellum-dependent motor learning task with different contexts to evaluate how MLIs are involved in this process. The results show that by suppressing dendritic Ca2+ signals in Purkinje cells, MLI activity coincident with climbing fiber-mediated excitation prevents the occurrence of learning when adaptation is not necessary. On the other hand, with error signals present, disinhibition onto Purkinje cells, mediated by MLI-MLI microcircuit, unlocked the ability of climbing fibers to induce plasticity and motor learning. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection