Astrocytes are the most abundant type of glial cell in the brain, required to ensure optimal neuronal functioning, neurogenesis, and brain vascular tone. Moreover, they play a crucial role in support of neuronal metabolism. The human brain utilizes around 20% of the energy consumed to ensure its proper function. Glucose, an important energy source for the brain, access the neuropil across the blood-brain barrier (BBB), and then is transported into astrocytes through their perivascular end-feet, where it can be stored as glycogen. Furthermore, lactate can be synthesized through glycogenolysis and then shuttled via monocarboxylate transporters (MCTs) to neurons to fuel their tricarboxylic acid (TCA) cycle. This mechanism is known as astrocyte-neuron lactate shuttle (ANLS) and is involved in learning and memory formation. Aging is associated with a decline of faculties such as memory, motor skills, and sensory perception. These deficits are not thought to be due to a substantial loss of neurons but rather changes at the level of connectivity, morphological changes, and white matter structure. In the present study, we aim to compare the glycogen distribution in layer I of the somatosensory cortex between adult (4 months old) and geriatric mice (24 months old). We carried out the visual analysis using Connectome Explorer, which allows us to explore, in real-time, brain reconstructions at the nanometric-level. Using the computational tool GLAM (Glycogen-derived Lactate Absorption Map), we can infer a probability map of the locations where astrocytic glycogen-derived lactate is most likely accessing the surrounding neurites. We analyzed and compared the probability maps on axons, dendrites, boutons, and spines to make a functional hypothesis about single compartments’ energy consumption. Our results indicate that aging brains have a more glycolytic metabolism, with fewer peaks facing mitochondria, and smaller glycogen granules.

Metabolic syndrome (MetS) is an association between obesity, dyslipidemia, hyperglycemia, hypertension, and insulin resistance. A relationship between MetS and vascular dementia was hypothesized. The purpose of this work is to investigate brain microanatomy alterations in obese Zucker rats (OZRs), as a model of MetS, compared to their counterparts lean Zucker rats (LZRs). 12-, 16-, and 20-weeks-old male OZRs and LZRs were studied. General physiological parameters and blood values were measured. Immunochemical and immunohistochemical techniques were applied to analyze the brain alterations. The morphology of nerve cells and axons, astrocytes and microglia were investigated. The blood–brain barrier (BBB) changes occurring in OZRs were assessed as well using aquaporin-4 (AQP4) and glucose transporter protein-1 (GLUT1) as markers. Body weight gain, hypertension, hyperglycemia, and hyperlipidemia were found in OZRs compared to LZRs. In the frontal cortex and hippocampus, a decrease of neurons was noticeable in the older obese rats in comparison to their age-matched lean counterparts. In OZRs, a reduction of neurofilament immunoreaction and gliosis was observed. The BBB of older OZRs revealed an increased expression of AQP4 likely related to the development of edema. A down-regulation of GLUT1 was found in OZRs of 12 weeks of age, whereas it increased in older OZRs. The behavioral analysis revealed cognitive alterations in 20-week-old OZRs. Based on these results, the OZRs may be useful for understanding the mechanisms through which obesity and related metabolic alterations induce neurodegeneration.

Os aspectos morfológicos dos neurônios e estruturas neurais, embora potencialmente importantes, têm recebido relativamente pouca atenção na literatura em neurociência. Este trabalho consiste numa substancial parte de um projeto em desenvolvimento no Grupo de Pesquisa em Visão Cibernética voltado para o estudo da relação formal/função neural. Mais especificamente, o presente trabalho dedica particular atenção para a síntese, modelagem e simulação de estruturas neurais morfologicamente realísticas. A tese se inicia com revisões bibliográficas sobre visão biológica e neurociência, direcionadas aos assuntos a serem aqui abordados. Começamos a descrição dos desenvolvimentos com um levantamento, avaliação e proposta de medidas neuromorfométricas adequadas para exprimir as propriedades mais representativas para nosso trabalho, tais como cobertura espacial, complexidade e decaimento eletrônico. Incluímos nessa parte a metodologia utilizada para a geração de neurônios artificiais bidimensionais estatisticamente semelhantes aos naturais. Apresenta-se também a extensão desta metodologia para o caso tridimensional, validada pela análise neuroinorfométrica dos neurônios gerados. Na seqüência, descrevemos o processo de geração de estruturas neurais compostas de neurônios. Considerando modelos com uma camada neural para a codificação de especificidade de orientação, mas sem levar em conta a forma neural, vários casos são simulados, utilizando gradientes na distribuição dos pesos sinápticos e distribuições regulares ou aleatórias (uniformes) dos neurônios na estrutura. A extensão dessas simulações utilizando estruturas que consideram mais detalhadamente a forma neural, usando agora neurônios artificiais gerados pelo método descrito nesta monografia, é apresentada na seqüência. Entre outros efeitos, mostramos que a extensão da arborização dendrítica é um fator determinante da taxa de convergência e seletividade nos modelos, e que gradientes na extensão das arborizações sinápticas são essenciais para a adequada codificação de orientações em módulos cêntricos contendo somatas aleatoriamente distribuídos. / The morphological aspects of neurons and neural structures, although potentially important, have received relatively little attention in the literature in neuroscience. This work consists in a substantial part of a project in development at the Cybernetic Vision Research Group, directed to the study of the form/function relationship. More specifically, the present work dedicates particular attention to the synthesis, modeling, and simulation of morphologically realistic neural structures. The thesis begins with a bibliographic review about biological vision and neuroscience, focusing on the subjects to be here considered. We start the description of the developments with the revision; evaluation and proposal of neuromorphometric measures adequate express the properties more representative to the work, such as spatial cover, complexity and electrotonic decay. We include in this part the methodology used for the generation of bidimensional artificial neurons statistically similar to natural ones. The extension of these developments to the tridimensional case, including their respective validation (performed in terms of neuromorphometric analysis of the generated neurons) is also presented. Next, we describe the generation process of neural structures composed of neurons. Using one-layer neural models for orientation specificity encoding, but without considering the neural shape, several cases are simulated, using gradients in the distribution of the synaptic weights and regular or random (uniform) distributions of the neurons in the structures. The extension of these simulations using structures that consider the neural form in more detail, composed of artificial neurons generated by the described method in this monograph is presented in the sequence. We show that the extension of the dendritic arborization is a determinant factor on the convergence rate and selectivity in the models, and that gradients in the extension of the synaptic arborizations are essentials for the adequate codification of orientations in centric models containing distributed random somata.

Os aspectos morfológicos dos neurônios e estruturas neurais, embora potencialmente importantes, têm recebido relativamente pouca atenção na literatura em neurociência. Este trabalho consiste numa substancial parte de um projeto em desenvolvimento no Grupo de Pesquisa em Visão Cibernética voltado para o estudo da relação formal/função neural. Mais especificamente, o presente trabalho dedica particular atenção para a síntese, modelagem e simulação de estruturas neurais morfologicamente realísticas. A tese se inicia com revisões bibliográficas sobre visão biológica e neurociência, direcionadas aos assuntos a serem aqui abordados. Começamos a descrição dos desenvolvimentos com um levantamento, avaliação e proposta de medidas neuromorfométricas adequadas para exprimir as propriedades mais representativas para nosso trabalho, tais como cobertura espacial, complexidade e decaimento eletrônico. Incluímos nessa parte a metodologia utilizada para a geração de neurônios artificiais bidimensionais estatisticamente semelhantes aos naturais. Apresenta-se também a extensão desta metodologia para o caso tridimensional, validada pela análise neuroinorfométrica dos neurônios gerados. Na seqüência, descrevemos o processo de geração de estruturas neurais compostas de neurônios. Considerando modelos com uma camada neural para a codificação de especificidade de orientação, mas sem levar em conta a forma neural, vários casos são simulados, utilizando gradientes na distribuição dos pesos sinápticos e distribuições regulares ou aleatórias (uniformes) dos neurônios na estrutura. A extensão dessas simulações utilizando estruturas que consideram mais detalhadamente a forma neural, usando agora neurônios artificiais gerados pelo método descrito nesta monografia, é apresentada na seqüência. Entre outros efeitos, mostramos que a extensão da arborização dendrítica é um fator determinante da taxa de convergência e seletividade nos modelos, e que gradientes na extensão das arborizações sinápticas são essenciais para a adequada codificação de orientações em módulos cêntricos contendo somatas aleatoriamente distribuídos. / The morphological aspects of neurons and neural structures, although potentially important, have received relatively little attention in the literature in neuroscience. This work consists in a substantial part of a project in development at the Cybernetic Vision Research Group, directed to the study of the form/function relationship. More specifically, the present work dedicates particular attention to the synthesis, modeling, and simulation of morphologically realistic neural structures. The thesis begins with a bibliographic review about biological vision and neuroscience, focusing on the subjects to be here considered. We start the description of the developments with the revision; evaluation and proposal of neuromorphometric measures adequate express the properties more representative to the work, such as spatial cover, complexity and electrotonic decay. We include in this part the methodology used for the generation of bidimensional artificial neurons statistically similar to natural ones. The extension of these developments to the tridimensional case, including their respective validation (performed in terms of neuromorphometric analysis of the generated neurons) is also presented. Next, we describe the generation process of neural structures composed of neurons. Using one-layer neural models for orientation specificity encoding, but without considering the neural shape, several cases are simulated, using gradients in the distribution of the synaptic weights and regular or random (uniform) distributions of the neurons in the structures. The extension of these simulations using structures that consider the neural form in more detail, composed of artificial neurons generated by the described method in this monograph is presented in the sequence. We show that the extension of the dendritic arborization is a determinant factor on the convergence rate and selectivity in the models, and that gradients in the extension of the synaptic arborizations are essentials for the adequate codification of orientations in centric models containing distributed random somata.

The anterior thalamic nuclei (ATN) are a critical part of an extended hippocampal system that supports key elements of episodic memory. Damage or disconnection of the ATN is a component of clinical conditions associated with severe anterograde amnesisa such as the Korsakoff’s syndrome, thalamic stroke, and neurodegenerative disorders. Previous studies have demonstrated that the ATN and hippocampus are often interdependent, and that ATN damage can result in ‘covert pathology’ in ostensibly healthy distal regions of the extended hippocampal system. Adult male rats with neurotoxic bilateral ATN lesions or sham surgery were post-operatively housed in an enriched environment or standard housing after a lesion-induced spatial working memory deficit had been established. These rats were retested on cross-maze and then trained in radial-arm maze spatial memory tasks. Other enriched rats received pseudo-training only after the enrichment period. The detailed neuromorphology of neurons was subsequently examined in the hippocampal CA1. Soma characteristics were also examined in the retrosplenial granular b cortex and the prelimbic cortex. In Experiment 1, ATN lesions produced clear deficits in both the cross-maze and radial-arm maze tasks and reduced hippocampal CA1 dendritic complexity, length, and spine density, while increasing the average diameter of the dendrites. Post-operative enrichment reversed the ATN lesion-induced deficits in the cross-maze and radial-arm maze, and returned CA1 basal and apical spine density to a level comparable to that of sham standard housed trained rats. The sham enriched rats exhibited improved radial-arm maze performance and increased CA1 branching complexity and spine density in both basal and apical arbors compared to sham standard housed rats. The neuromorphological changes observed in the enriched ATN and sham rats may be in part responsible for the spatial working memory improvements observed. Experiment 2 provided support for this contention by demonstrating that the CA1 spine changes were explicitly relevant to spatial learning and memory, because trained enriched sham and ATN rats had increased spines, particularly in the basal tree when compared to closely comparable pseudo-trained enriched rats. Interestingly, spatial memory training increased the numbers of both thin and mushroom spines, whereas enrichment was only associated with an increase in thin spines. In Experiment 3, ATN lesions increased cell body size in layer II of the retrosplenial granular b cortex, whereas enrichment decreased cell body size in layer V of this region. Neither ATN lesions nor enrichment had any effect on cell body morphology in the prelimbic cortex. The current research provides some of the strongest evidence to date of ATN and hippocampal interdependence within the extended hippocampal system, and provides the first evidence of neuromorphological correlates of recovery after ATN lesions.