The influence of play behavior on the brain was investigated through plasticity and metaplasticity methodology. Regions in both cortical and sub-cortical areas were investigated. Animals in both studies either experienced play with juvenile partners or did not experience play by being paired with an adult. Play experience alone was shown to affect the plasticity in the prefrontal cortex, although it did not show structural changes to sub-cortical regions. If animals were given nicotine after play experiences, the affects of play in the prefrontal cortex were abolished. In addition, playful behaviors appear to prime some sub-cortical regions of the brain for expression of later plasticity. Thus, play appears to alter the structure of multiple brain areas, but do so in different ways. / ix, 67 leaves ; 29 cm

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

The best for PhD thesis in the Faculties of Arts, Architecture, Business & Economics, Education, Law and Social Sciences (Universityof Hong Kong), Li Ka Shing prize, 2006-2007 / published_or_final_version / abstract / Psychology / Doctoral / Doctor of Philosophy

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 interplexiform cells(IP cells) are the most recently discovered neurons in the retina and their function is to provide centrifugal feedback in retina. The anatomical structure of the IP cells has been well studied, but the function of these neurons is largely unknown. I systematically studied the excitatory and inhibitory inputs from IP cells in salamander retina. I found that L-EPSCs in IP cells are mediated by AMPA and NMDA receptors; in addition, L-IPSCs are mediated by glycine receptors and GABAC receptors. In response to light, IP cells reaction potentials transiently at the onset and onset of light stimulation. The major neural transmitter of IP cells in salamander retina is glycine. We also studied the distribution and function of glycine transporters. Our result indicates that GlyT1- and GlyT2-like transporters were present in Muller cells and neurons. The glycine feedback at outer plexiform layer (OPL) has effects on both the bipolar cell dendrites and rod photoreceptor terminals. At bipolar cell dendrites, glycine selectively depolarizes rod-dominant On-bipolar cells, and hyperpolarizes Off- bipolar cells. At rod photoreceptor terminals, 10 M glycine activates voltage-gated Ca2+ channels. These effects facilitated glutamate vesicle release in photoreceptors. It increases the sEPSC in OFF bipolar cells. The combined effect of glycine at rod terminals and bipolar cell dendrites leads to enhanced dim light signal transduction in the rod photoreceptor to ganglion cell pathway. This study provides a model that displays the function of centrifugal feedback through IP cells in the retina. / by Zheng Jiang. / Thesis (Ph.D.)--Florida Atlantic University, 2009. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2009. Mode of access: World Wide Web.

Dramatic changes occur across childhood and adolescence in the activity and connectivity of an amygdala-medial prefrontal cortex circuit critical for emotional learning and regulation. However, little is currently known about how neuroplasticity within the circuit changes during development in the human. Experiences that occur during developmental sensitive periods of increased neuroplasticity have the capacity to sculpt neural function with lifelong consequences for cognition and behavior, though. This dissertation will therefore investigate when and how experience may shape amygdala-medial prefrontal cortex functional circuitry (Aim 1) and what the implications of experience-dependent circuitry development are for emotion regulation behaviors (Aim 2) across childhood, adolescence, and adulthood in three studies. Study 1 (previously published as Gabard-Durnam, Gee et al., 2016) posits and tests the long-term phasic molding hypothesis that tonic amygdala-prefrontal cortex functional connectivity, the functional architecture of the brain, is shaped during development by recurring stimulus-elicited connectivity in the circuitry using prospective examination of these connectivities’ development across childhood and adolescence. Study 1 also tests whether the ability of amygdala-prefrontal cortex stimulus-elicited connectivity to shape the amygdala-prefrontal cortex resting-state functional architecture changes across development, reflecting changing plasticity of the circuitry. Study 2 examines how the timing and duration of an early adverse experience, parental deprivation, interacts with genetically-driven differences in neuroplasticity levels indexed by the Brain-Derived Neurotrophic Factor val66met polymorphism to influence the developmental trajectory of amygdala-prefrontal cortex functional architecture using a population of previously-institutionalized children and adolescents and a never-institutionalized comparison sample. Study 2 further examines how the experience- and plasticity-related changes to the functional architecture influence both concurrent and future internalizing symptomatology across childhood and adolescence. Study 3 builds on the first two developmental studies by explicitly testing whether childhood is a sensitive period for medial prefrontal cortex-mediated regulatory signal learning through a retrospective design in adults. Study 3 additionally assesses the effects of developmental experience on adult emotion regulation behavior and physiology. My findings at the levels of brain circuitry, behavior, physiology, and genetics together delineate a period of increased sensitivity to the environment within prefrontal cortex-amygdala functional circuitry from infancy through childhood, modifiable by genetically-conferred variation in plasticity and the nature of the early environment. Moreover, experiences occurring during the sensitive period have consequences for future emotion regulation behavior both during development and lasting into young adulthood. Together, these findings demonstrate how experience-dependent development has enduring effects on amygdala-prefrontal cortex circuitry function and affective behavior.

Le syndrome d’apnées obstructives du sommeil (SAOS) se caractérise par des collapsus récurrents des voies aériennes supérieures pendant le sommeil, entraînant des épisodes d’hypoxie/hypercapnie. Par ces variations gazeuses, le SAOS entraîne des altérations cardiorespiratoires, représentant ainsi un danger de vie pour les patients, mais dont certaines sont moins marquées chez les patientes. La prévalence chez les hommes est plus élevée que celle des femmes pré-ménopausées et elle est augmentée par l’obésité.L’objectif de ce doctorat était de caractériser les dimorphismes sexuels dans la neuroplasticité associée au SAOS, à l’origine des altérations cardiorespiratoires. Pour cela, nous avons soumis des souris à un protocole d’hypoxie intermittente chronique (HIC), ce modèle récapitulant l’hypoxie récurrente du SAOS. Dans l’encéphale de ces souris, nous avons pu apprécier des atteintes différentielles entre les souris mâles et femelles au sein de structures cardiorespiratoires avec un profil de neuroplasticité réservé aux femelles qui pourrait atténuer chez ces dernières les effets de l’HIC. Cela ouvre des pistes explicatives des différences sexuelles retrouvées chez les patients et patientes SAOS. Nous avons également caractérisé une souche de souris obèses (New Zealand Obese) en tant que modèle du SAOS. Nous fournissons ainsi le premier modèle murin naturel du SAOS lié à l’obésité. Enfin, ce travail contribue à une meilleure connaissance des différences sexuelles observées dans le SAOS et fournit un modèle facilement accessible qui offre la possibilité de réaliser des études plus complètes de la pathologie du SAOS. / The obstructive sleep apnea syndrome (OSAS) is characterized by recurrent collapse of the upper airways during sleep, generating episodes of hypoxia/hypercapnia. Thus, OSAS leads to life-threatening cardiorespiratory comorbidities, but of which some are less severe in female patients. The prevalence in men is higher than that of pre-menopausal women and it is increased by obesity. This doctoral thesis aimed to characterize sex differences in the neuroplasticity related to cardi-orespiratory comorbidities found in OSAS. In this context, we submitted mice to a protocol of chronic intermittent hypoxia, a model that recapitulates episodic hypoxia of OSAS. On isolated brain sections, we observed differential implication of cardiorespiratory structures between male and female mice with a specific neuroplastic pattern in females that could possibly explain sex differences observed in OSAS patients. In parallel, we have characterized an obese mouse strain (New Zealand Obese) as a model of OSAS. Thus, we provide the first naturel mouse model for OSAS related to obesity. The work presented in this thesis provides better understanding of sex differences observed in OSAS and provides a new model of OSAS that should allow more complete studies of the pathology of OSAS.

Dauer larva formation in C. elegans is a life-history polyphenism that relies on the function of several pathways, including insulin, TGFβ and nuclear hormone receptor signaling. The downstream effectors of these pathways, DAF-16/FOXO, DAF-3/Co-Smad and DAF-12/VDR, are transcription factors (DAF TFs) with broad or ubiquitous expression patterns, null mutations in which result in the inability to form dauers regardless of environmental conditions. In preparation for the dauer diapause, all tissues of the worm undergo extensive morphological and functional remodeling in a coordinated manner. The broad goal of my thesis is to understand how these transcription factors act in different tissues of the worm to regulate the dauer-specific tissue remodeling and gene expression changes. In addition to characterizing dynamic expression pattern of chemosensory GPCR genes in dauer, which revealed an additional layer of plasticity and provided novel entry points to studying remodeling in distinct neuron classes and non- neuronal tissues, I have developed molecular tools – conditional alleles of the daf TFs – that allowed me to address the question of tissue-specificity and cell-autonomy of the DAF TFs in a previously inapproachable way. I have found that DAF TFs act in both cell-autonomous (DAF-16 in neurons, intestine, pharynx) and non-autonomous manner (DAF-16 in the pharynx) to control dauer tissue remodeling. Unlike DAF-16 and DAF-12, the function of DAF-3 in the dauer decision appears to be largely determined by its action in neurons, and specifically in sensory neurons. The three TFs also differ in their roles in pharynx remodeling: while DAF-16 controls dauer pharyngeal morphology and activity both cell-autonomously and non- autonomously, DAF-12 or DAF-3 depletion from pharyngeal muscle does not affect the dauer pharyngeal phenotypes. Yet, all three TFs are required continuously throughout all tissues to maintain the dauer state, once the decision to enter dauer has been made. This work is a first attempt to characterize tissue-specific roles of all transcriptional effectors of the dauer pathways in a systematic way, and contributes to a fundamental understanding of a polyphenic developmental switch regulated by highly conserved molecular pathways.

A Bell in the Storm - Persistent unexplained pain and the language of the uncanny in the creative neurophenomenal reference is a doctoral work comprised of three parts. Part 1 is an exegesis Persistent unexplained pain and the language of the uncanny in the creative neurophenomenal reference; Part 2 is The Plays, A Bell in the Storm (produced by deckchair theatre in May, 2005) and the radio play To Fall Without Landing (produced by the Australian Broadcasting Commission for Radio National in October 2005); and, Part 3 the book of monochord poems, Secrets of the Driftwood.

Thesis (Ph. D.)--University of Oregon, 2006. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 124-134). Also available for download via the World Wide Web; free to University of Oregon users.