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Recent evidence indicates that the mature neocortex retains a higher degree of plasticity than traditionally assumed. Up- and down-regulation of synaptic strength, long-term potentiation (LTP) and long-term depression (LTD), is thought to be the primary mechanism mediating experience-dependent plasticity of cortical networks. The present thesis investigate factors that regulate adult cortical plasticity, focusing on the role of neuromodulators, recent sensory experience, and different anatomical divisions of the cortex in influencing synaptic strength. First, I investigated the role of the neuromodulator histamine in gating plasticity in the primary visual cortex (V1) of urethane anesthetized adult rats. Histamine applied locally in V1 produced an enhancement of LTP elicited by theta burst stimulation (TBS) of dorsal lateral geniculate nucleus (dLGN) and allowed a sub-threshold TBS to produce stable LTP. Second, the impact of visual deprivation on LTP in V1 was assessed. Animals that received 2 and 5 hr dark exposure showed greater potentiation of field potentials when stimulated though retinal light flashes or weak TBS of the dLGN, which failed to induce LTP in control animals kept in continuous light. Third, I performed a detailed characterization of LTP induced by different TBS protocols, recording in either the monocular or binocular segment of both V1 hemispheres (i.e., ipsi- and contralateral to the stimulated dLGN). Stronger, NMDA receptor-independent LTP was found in the contralateral V1. Interestingly, weak TBS induced LTD that was NMDA receptor-dependent in the ipsilateral V1. Furthermore, a lower LTP induction threshold was observed in the binocular than the monocular segment of ipsilateral V1. Lastly, I investigated cholinergic modulation of sensory-induced activity in the barrel cortex. Basal forebrain stimulation enhanced multi-unit activity elicited by whisker deflection, an effect that was more pronounced for weaker response driven by a secondary whisker than principal whisker deflection. This thesis demonstrates that neocortical plasticity consists of multiple forms of synaptic modification. Adult cortical plasticity is greatly influenced by preceding activity of the synapse by various neuromodulator systems, and by anatomical subdivisions within primary sensory cortex fields. Together, these mechanisms may facilitate the detection, amplification, and storage of inputs to primary sensory fields of the neocortex. / Thesis (Ph.D, Psychology) -- Queen's University, 2010-04-29 14:02:30.742

The notion that learning and memory processes are highly dependent on central cholinergic neurotransmission has been widely accepted. However, studies documenting the importance of Acetylcholine (ACh) in attention have led some to suggest that attention impairments may underlie the deficits in learning and memory resulting from cholinergic disruptions. Using a visual discrimination task, I attempted to discern whether performance impairments by Scopolamine were predominantly due to the importance of muscarinic receptor integrity in attention, or memory consolidation in learning. Rats were trained in a visual discrimination task using a Y-shaped water maze apparatus. To successfully navigate to a hidden platform located in one of the two goal arms, rats learned to discriminate between 2 distinct visual cues, indicating the platform’s presence (CS+) or absence (CS-), respectively. Following task acquisition, testing continued using a combination of Regular trials (RT; both CS+ and CS- present) and Probe trials (PT; only one of the cues present). Results indicated that performance on PT was impaired due to greater task difficulty under conditions of reduced information, while Scopolamine (1 mg/kg) further impacted PT performance without affecting RTs. In a second experiment, PTs were administered with the platform present to provide reinforcement and a learning opportunity. Animals still exhibited poorer PT performance, but rapidly learned to rely on a single cue for accurate platform localization. Interestingly, this learning was not apparent under conditions of Scopolamine treatment (1 mg/kg), even though RT performance was completely unaffected. To examine experience-dependent changes in neuronal responding after visual discrimination learning, a subset of animals were anesthetised and visual evoked potentials (VEPs) in V1 and area CA1 of the hippocampus were recorded in response to CS+, CS-, and novel stimuli. In both the V1 and CA1, the VEP amplitudes elicited to familiar and novel stimuli were not significantly different. First, these experiments demonstrate the importance of the cholinergic system in sustaining visual attention and acquiring a new single-cue strategy. Furthermore, the null electrophysiology findings do not rule out the plastic response properties of the mature V1 and CA1, but remind us of the complex nature of memory encoding in the brain. / Thesis (Master, Psychology) -- Queen's University, 2011-09-16 13:50:24.045

A series of studies is described here which explore the functional organisation of face- and object-processing neurones in the adult vervet monkey brain. This fundamental issue in high-level vision is addressed by the use of a novel molecular mapping technique that was developed for this purpose. / In the first study, the temporal dynamics of c-fos and zif268 expression were delineated in detail in the rat visual cortex. Knowing the precise temporal parameters of up-regulation (after onset of sensory stimulation) and down-regulation (after offset of sensory stimulation) of these genes was integral to optimising the temporal aspects of the stimuli to be used for subsequent mapping experiments. This study provided the critical information for devising stimuli with corresponding temporal parameters to those of c-fos or zif268 so that one could take advantage of the disparity between the expression of their mRNA and protein products in order to visualise activated neurones. / In the second study, the newly developed molecular mapping technique was validated in the rat auditory, visual and multisensory systems. First, bimodal audiovisual stimuli were designed using the data obtained from the first study. Then, through the combined histological detection of the mRNA and protein products of zif268, discrete populations of neurones responsive to either component of the bimodal stimulus were visualised. It was also observed that a third population of neurones was found that responded to the stimulation through both sensory modalities. The combined results from these two studies set the stage for addressing the issue of the organisation of face- and object-selective neurones of the inferior temporal cortex in the vervet monkey brain. / In the third study, the functional organisation of face- and object-selective neurones was examined using the molecular mapping technique. Based on the data gathered from the first two studies, suitable stimuli containing two distinct object classes (conspecific faces and non-face familiar objects) were designed with appropriate temporal parameters. / Finally, the last study provided an opportunity to address the issue of hemispheric asymmetry of function in the context of face processing in the non-human primate brain. Results support the notion that there may indeed be phylogenetic explanations for the hemispheric asymmetry observed in the human brain.

The current knowledge of the visual pathways in primates includes the patterns of projection from the retina through the dorsal lateral geniculate nucleus (dLGN) to the striate cortex (V1) and the extra-striate projections towards the dorsal and ventral streams. Cells with short wavelength sensitive cone (S-cone) inputs in the dLGN have been studied extensively in New World marmosets but not in Old World macaques. This thesis presents results from studies in the macaque monkey which are more relevant to humans since humans are closer in evolution to Old World than New World monkeys. / The spatial, temporal, chromatic and orientation preferences of neurons in the dLGN of the macaque were investigated by electrophysiological methods. The physiological findings of cells with S-cone inputs were compared to cells with opponent inputs from the long and medium wavelength sensitive cones (L-cones & M-cones, respectively). The cells receiving S-cone inputs (blue-yellow or B-Y cells) preferred lower spatial frequencies than the cells with opponent L-cone and M-cone inputs (red-green or R-G cells). Orthodromic latencies from optic chiasm stimulation were measured where possible to distinguish differences in conduction velocity between the cell groups. Although the B-Y cells usually had longer latencies than R-G cells, there wasconsiderable overlap between the cell groups. / The recorded cells were localised through histological reconstruction of dLGN sections stained for Nissl substance. The distribution of B-Y cells within the dLGN was compared to the distribution of R-G cells. The majority of B-Y cells were located within the intercalated koniocellular layers as well as the koniocellular bridges (extensions of the koniocellular layers into the adjacent parvocellular layers). The B-Y cells were also largely segregated within the middle dLGN layers (K3, P3, K4 & P4). The R-G cells were mainly concentrated within the parvocellular layers (P3, P4, P5 & P6) and were evenly distributed throughout the middle and outer layers of the dLGN. / The study also included recordings from the extra-striate middle temporal area (MT) to determine whether a fast S-cone input exists from the dLGN to area MT which bypasses V1. The pattern of cone inputs to area MT neurons was investigated before and during inactivation of V1. The inactivation was done through reversible cooling with a Peltier thermocouple device or focal inactivation with y-amino butyric acid (GABA) iontophoresis. Precise inactivation of V1 to the topographically matching visual fields of the recording sites in area MT revealed a preservation of all three coneinputs in many cells. The subcortical sources of these preserved inputs are discussed with their relevance to blindsight, which is the limited retention of visual perception after V1 damage. Analysis of the latencies of area MT cells revealed a rough segregation into latencies faster or slower than 70 ms. Cells both with and without a significant change in response during V1 inactivation were present in each group. The findings reported in this thesis indicate that some of the preserved inputs in area MT during V1 inactivation may be carried by a direct input from the dLGN which bypasses V1.

De nombreux arguments, issus notamment de la neurophysiologie visuelle, suggèrent que la perception visuelle d'une scène débute par une extraction des différentes fréquences spatiales en suivant une stratégie d'analyse « coarse-to-fine ». L'analyse rapide de l'information grossière en basses fréquences spatiales (BFS) fournirait un aperçu global de la de la scène qui serait, ensuite, affinée par l'analyse plus tardive de l'information fine en hautes fréquences spatiales (HFS). L'objectif de cette thèse est de spécifier les mécanismes neuro-fonctionnels et cognitifs du traitement des fréquences spatiales et des scènes naturelles et leur évolution au cours du vieillissement normal et pathologique. Dans une première étude en IRMf (Expérience 1), nous avons montré la coexistence, au niveau du cortex occipital, d'un traitement rétinotopique et hémisphérique des fréquences spatiales. Par ailleurs, nous avons montré que des régions sélectives aux scènes, au sein du gyrus parahippocampique et du cortex retrosplenial, étaient également impliquées dans le traitement des fréquences spatiales. Dans les études IRMf suivantes (Expériences 2, 3 et 4), nous nous sommes particulièrement intéressés au traitement des fréquences spatiales et à la stratégie d'analyse « coarseto- fine » dans ces régions sélectives. Dans la seconde partie de ces travaux, nous avons montré que la stratégie de catégorisation « coarse-to-fine » observée chez le jeune adulte sain, devenait flexible avec l'âge (Expérience 5). Afin de préciser les interactions rétino-corticales, nous avons étudié les performances de catégorisation de patients atteints de dégénérescence maculaire liée à l'âge, pathologie caractérisée par des lésions de la rétine centrale supposée à l'origine de la voie de traitement des HFS. Nous avons démontré un déficit comportemental (Expériences 6 et 7) du traitement des HFS, associé à une hypoactivité du cortex occipital chez ces patients (Expérience 8). Ces travaux permettent de préciser les mécanismes impliqués dans la perception de scènes. / As suggested by evidence from visual neurophysiology, scene perception could begin by the extraction of different spatial frequencies following a “coarse-to-fine” analysis. The rapid analysis of coarse information in low spatial frequencies (LSF) would provide a global overview of the scene which would then be refined by later analysis of fine information in high spatial frequencies (HSF). The aim of this thesis is to specify the neuro-functional and cognitive mechanisms of spatial frequency and natural scene processing as well as their evolution during normal and pathological aging. In a first fMRI study (Experiment 1), we showed the coexistence of retinotopic and hemispheric processing for spatial frequencies in occipital cortex. In addition, we showed that scene selective regions in the parahippocampal gyrus and retrosplenial cortex were also involved in the processing of spatial frequencies. Therefore, in the following fMRI studies (Experiments 2, 3 and 4), we were particularly interested in spatial frequency processing and "coarse-to-fine" analysis in these selective regions. In the second part of this work, we showed that the “coarse-to-fine” strategy observed in healthy young adults becomes flexible with increasing age (Experiment 5). To clarify the retina-cortex interactions, we studied the categorization performance of patients with age-related macular degeneration. This pathology is characterized by lesions of the central retina, which is thought to be the origin of the visual pathway conveying HSF. We have demonstrated a behavioral deficit (Experiments 6 and 7) of HSF processing linked to hypoactivity of occipital cortex in these patients (Experiment 8). These works clarify the mechanisms involved in scene perception.

Orientador: Roberto J. M. Covolan / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Fisica Gleb Wataghin / Made available in DSpace on 2018-08-14T22:08:05Z (GMT). No. of bitstreams: 1 UcedaOtero_EnriquePorfirio_D.pdf: 7252585 bytes, checksum: 3b003f17c9e6e0a72174f7dbd766bd36 (MD5) Previous issue date: 2009 / Resumo: A ativação cerebral envolve um complexo arranjo de processos neuronais, metabólicos e vasculares, que se estende do nível molecular e celular ao nível de extensas zonas corticais. O processo de disparo neuronal requer a restauração de gradientes iônicos e a reciclagem de neurotransmissores, o que implica em um custo energético suprido na forma de trifosfato de adenosina (ATP). A principal via de síntese do ATP é a via aeróbica e se dá pelo metabolismo oxidativo da glicose. Para tanto, o metabolismo cerebral depende de um constante suprimento de glicose e oxigênio, que é mantido pela circulação sanguínea através de uma complexa rede de vasos, que compõe o sistema vascular cerebral. A regulação desse complexo sistema neurovascular-metabólico é objeto de intensa investigação e está no centro do trabalho aqui apresentado, que visa o mapeamento do córtex visual através de uma abordagem multimodal envolvendo eletroencefalografia (EEG) e espectroscopia óptica na região do infravermelho próximo (NIRS - near infrared spectroscopy). O objetivo central deste trabalho foi o desenvolvimento de uma metodologia que permitisse a realização de medidas simultâneas da atividade neuronal, via EEG, e das alterações vasculares associadas a essas, via NIRS. Através desta técnica foi estudado o córtex visual de indivíduos adultos saudáveis, através da apresentação de estímulos modulados em frequência e em contraste. Esses experimentos foram realizados utilizando visão tanto binocular quanto monocular, sendo esta última para cada olho separadamente. Os estudos de EEG, realizados com eletrodos posicionados em O1 e O2, permitiram registrar claras alterações dos ritmos cerebrais alfa e beta em correlação com as variações de contraste e frequência do estímulo visual. As medidas ópticas, realizadas através do escalpo com optodos colocados estímulo dos eletrodos, permitiram registrar respostas hemodinâmicas bastante enfáticas, que mostraram alguma variabilidade em correlação com o contraste e a frequência dos estímulos visuais utilizados. Os resultados obtidos demonstram a viabilidade de se estudar o acoplamento neurovascular-metabólico em humanos através de uma abordagem multimodal não-invasiva, utilizando-se um sistema conjugado NIRS-EEG / Abstract: Brain activation involves a complex arrangement of neuronal, metabolic and vascular processes, which goes from molecular and cellular level to the level of extensive cortical and subcortical zones. The process of neuronal firing requires the restoration of ionic gradients and neurotransmitter recycling, which implies supplying energy in the form of Adenosine Triphosphate (ATP). ATP synthesis follows mainly the aerobic way and occurs by the oxidative metabolism of glucose. Therefore, the cerebral metabolism depends on a constant supply of glucose and oxygen, which is maintained by the blood circulation through the complex networks of blood vessels that compose the cerebral vascular system. The regulation of this complex neurovascular-metabolic system is object of intense investigation and is in the center of the work presented here, that aims to investigate the human visual system through a multimodal boarding integrating electroencephalography (EEG) and near infrared spectroscopy (NIRS). The central objective of this work was the development of a methodology that would allow simultaneous measurements of the neuronal activity, via EEG, and of the vascular changes associated to these, via NIRS. Through this technique, we studied the visual cortex of healthy adults, through the presentation of stimuli modulated alternatively in frequency and contrast. These experiments were performed for both binocular and monocular vision, being the latter for both eyes. The studies of EEG were performed with electrodes positioned in O1 and O2 and allowed to register clear alterations of alpha and beta brain rhythms in correlation with the contrast and frequency variations of the visual stimulus. The optical measurements were performed through the skull with optodes placed around the electrodes and allowed to record hemodynamic responses whose variability was also related to the contrast and frequency modulations of the visual stimuli. The obtained results demonstrate the feasibility of applying a conjugated NIRS-EEG system as a multimodal approach to study the neurovascular-metabolic coupling in humans / Doutorado / Física Médica / Doutor em Ciências

A neurociência computacional é uma vasta área que tem como objeto de estudo o entendimento ou a emulação da dinâmica cerebral em diversos níveis. Neste trabalho atenta-se ao estudo da dinâmica de neurônios, os quais, no consenso atual, acredita-se serem as unidades fundamentais do processamento cerebral. A importância do estudo sobre o comportamento de neurônios se encontra na diversidade de propriedades que eles podem apresentar. O estudo se torna mais rico quando há interações de sistemas internos ao neurônio em diferentes escalas de tempo, criando propriedades como adaptação, latência e comportamento em rajada, o que pode acarretar em diferentes papéis que os neurônios podem ter na rede. Nesta dissertação é feita uma análise sob o ponto de vista de sistemas dinâmicos e de análise de sensibilidade de seis modelos ao estilo de Hodgkin-Huxley e compartimentais de neurônios encontrados no córtex visual primário de mamíferos. Esses modelos correspondem a seis classes eletrofisiológicas de neurônios corticais e o estudo feito nesta dissertação oferece uma contribuição ao entendimento dos princípios de sistemas dinâmicos subjacentes a essa classificação. / Computational neuroscience is a vast scientific area which has as subject of study the unsderstanding or emulation of brain dynamics at different levels. This work studies the dynamics of neurons, which are believed, according to present consensus, to be the fundamental processing units of the brain. The importance of studying neuronal behavior comes from the diversity of properties they may have. This study becomes richer when there are interactions between distintic neuronal internal systems, in different time scales, creating properties like adaptation, latency and bursting, resulting in different roles that neurons may have in the network. This dissertation contains a study of six reduced compartmental conductance-based models of neurons found in the primary visual cortex of mammals under the dynamical systems and sensitivity analysis viewpoints. These models correspond to six eletrophysiological classes of cortical neurons and this dissertation offers a contribution to the understanding of the dynamical-systems principles underlying such classification.

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