Development of brain function is instructed by both genetically-determined processes (nature) and environmental stimuli (nurture). The relative importance of nature and nurture is a major question in developmental neurobiology. In this dissertation, I investigated the role of visual experience in the development and plasticity of the visual pathway. Each neuron that receives visual input responds to a specific area of the visual field- their receptive field (RF). Developmental refinement reduces RF size and underlies visual acuity, which is important for survival. By rearing Syrian hamsters (Mesocricetus auratus) in constant darkness (dark rearing, DR) from birth, I investigated the role of visual experience in RF refinement and plasticity. Previous work in this lab has shown that developmental refinement of RFs occurs in the absence of visual experience in the superior colliculus (SC), but that RFs unrefine and thus enlarge in adulthood during chronic DR. Using an in vivo electrophysiological approach, I show that, contrary to a widely held view, visual experience is not necessary for refinement of RFs in primary visual cortex (V1). In both SC and V1, RFs refine by postnatal day (P) 60, but enlarge by P90 with chronic DR. One week of visual experience was sufficient to prevent RF enlargement in SC and V1. How normal sensory experience prevents plasticity in mature circuits is not well understood. Using an in vitro electrophysiological approach, I demonstrated that GABAergic inhibition is reduced in DR SC, which in turn affects short-term (but not long-term) synaptic plasticity. The level of GABABR-mediated short-term synaptic depression (STD) that occurs during high-frequency afferent stimulation, such as occurs during vision, is reduced by DR. Using a computational model of RF size, I propose that, in addition to the effect of reduced inhibition, reduced STD of excitation could contribute to enlarged RFs. This work provides insight into mechanisms of development and plasticity of the nervous system. How plasticity is restricted in mature circuits is of fundamental importance in neuroscience and could instruct therapies to prevent maladaptive plasticity in disease and to enhance recovery of function in adults.

No description available.

Thesis (Ph. D.)--University of California, San Diego, 2007. / Title from first page of PDF file (viewed January 8, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 112-124).

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 4 uppsatser.

Diss. Linköping : Univ., 2003.

The question of how shape is represented is of central interest to understanding visual processing in cortex. While tuning properties of the cells in early part of the ventral visual stream, thought to be responsible for object recognition in the primate, are comparatively well understood, several different theories have been proposed regarding tuning in higher visual areas, such as V4. We used the model of object recognition in cortex presented by Riesenhuber and Poggio (1999), where more complex shape tuning in higher layers is the result of combining afferent inputs tuned to simpler features, and compared the tuning properties of model units in intermediate layers to those of V4 neurons from the literature. In particular, we investigated the issue of shape representation in visual area V1 and V4 using oriented bars and various types of gratings (polar, hyperbolic, and Cartesian), as used in several physiology experiments. Our computational model was able to reproduce several physiological findings, such as the broadening distribution of the orientation bandwidths and the emergence of a bias toward non-Cartesian stimuli. Interestingly, the simulation results suggest that some V4 neurons receive input from afferents with spatially separated receptive fields, leading to experimentally testable predictions. However, the simulations also show that the stimulus set of Cartesian and non-Cartesian gratings is not sufficiently complex to probe shape tuning in higher areas, necessitating the use of more complex stimulus sets.

The primary visual cortex (V1) has long been considered the main low level visual analysis area of the brain. The classical view is of a feedfoward system functioning as an edge detector, in which each cell has a receptive field (RF) and a preferred orientation. Whilst intuitive, this view is not the whole story. Although stimuli outside a neuron’s RF do not result in an increased response by themselves, they do modulate a neuron’s response to what’s inside its RF. We will refer to such extra-RF effects as contextual modulation. Contextual modulation is thought to underlie several perceptual phenomena, such as various orientation illusions and saliency of specific features (such as a contour or differing element). This gives a view of V1 as more than a collection of edge detectors, with neurons collectively extracting information beyond their RFs. However, many of the accounts linking psychophysics and physiology explain only a small subset of the illusions and saliency effects: we would like to find a common principle. So first, we assume the contextual modulations experienced by V1 neurons is determined by the elastica model, which describes the shape of the smoothest curve between two points. This single assumption gives rise to a wide range of known contextual modulation and psychophysical effects. Next, we consider the more general problem of encoding and decoding multi-variate stimuli (such as center surround gratings) in neurons, and how well the stimuli can be decoded under substantial noise levels with a maximum likelihood decoder. Although the maximum likelihood decoder is widely considered optimal and unbiased in the limit of no noise, under higher noise levels it is poorly understood. We show how higher noise levels lead to highly complex decoding distributions even for simple encoding models, which provides several psychophysical predictions. We next incorporate more updated experimental knowledge of contextual modulations. Perhaps the most common form of contextual modulations is center surround modulation. Here, the response to a center grating in the RF is modulated by the presence of a surrounding grating (the surround). Classically this modulation is considered strongest when the surround is aligned with the preferred orientation, but several studies have shown how many neurons instead experience strongest modulation whenever center and surround are aligned. We show how the latter type of modulation gives rise to stronger saliency effects and unbiased encoding of the center. Finally, we take an experimental perspective. Recently, both the presence and the underlying mechanisms of contextual modulations has been increasingly studied in mice using calcium imaging. However, cell signals extracted with calcium imaging are often highly contaminated by other sources. As contextual effects beyond center surround modulation can be subtle, a method is needed to remove the contamination. We present an analysis toolbox to de-contaminate calcium signals with blind source separation. This thesis thus expands our understanding of contextual modulation, predicts several new experimental results, and presents a toolbox to extract signals from calcium imaging data which should allow for more in depth studies of contextual modulation.

Made available in DSpace on 2014-12-17T15:29:22Z (GMT). No. of bitstreams: 1 SergioACO_TESE.pdf: 4589227 bytes, checksum: 062baf399b5377e444d02b747586f12b (MD5) Previous issue date: 2014-03-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Desde os descobrimentos pioneiros de Hubel e Wiesel acumulou-se uma vasta literatura descrevendo as respostas neuronais do c?rtex visual prim?rio (V1) a diferentes est?mulos visuais. Estes est?mulos consistem principalmente em barras em movimento, pontos ou grades, que s?o ?teis para explorar as respostas dentro do campo receptivo cl?ssico (CRF do ingl?s classical receptive field) a caracter?sticas b?sicas dos est?mulos visuais como a orienta??o, dire??o de movimento, contraste, entre outras. Entretanto, nas ?ltimas duas d?cadas, tornou-se cada vez mais evidente que a atividade de neur?nios em V1 pode ser modulada por est?mulos fora do CRF. Desta forma, ?reas visuais prim?rias poderiam estar envolvidas em fun??es visuais mais complexas como, por exemplo, a separa??o de um objeto ou figura do seu fundo (segrega??o figura-fundo) e assume-se que as conex?es intr?nsecas de longo alcance em V1, assim como as conex?es de ?reas visuais superiores, est?o ativamente envolvidas neste processo. Sua poss?vel fun??o foi inferida a partir da an?lise das varia??es das respostas induzidas por um est?mulo localizado fora do CRF de neur?nios individuais. Mesmo sendo muito prov?vel que estas conex?es tenham tamb?m um impacto tanto na atividade conjunta de neur?nios envolvidos no processamento da figura quanto no potencial de campo, estas quest?es permanecem pouco estudadas. Visando examinar a modula??o do contexto visual nessas atividades, coletamos potenciais de a??o e potenciais de campo em paralelo de at? 48 eletrodos implantados na ?rea visual prim?ria de gatos anestesiados. Estimulamos com grades compostas e cenas naturais, focando-nos na atividade de neur?nios cujo CRF estava situado na figura. Da mesma forma, visando examinar a influ?ncia das conex?es laterais, o sinal proveniente da ?rea visual isot?pica e contralateral foi removido atrav?s da desativa??o revers?vel por resfriamento. Fizemos isso devido a: i) as conex?es laterais intr?nsecas n?o podem ser facilmente manipuladas sem afetar diretamente os sinais que est?o sendo medidos, ii) as conex?es inter-hemisf?ricas compartilham as principais caracter?sticas anat?micas com a rede lateral intr?nseca e podem ser vistas como uma continua??o funcional das mesmas entre os dois hemisf?rios e iii) o resfriamento desativa as conex?es de forma causal e revers?vel, silenciando temporariamente seu sinal, permitindo conclus?es diretas a respeito da sua contribui??o. Nossos resultados demonstram que o mecanismo de segmenta??o figurafundo se reflete nas taxas de disparo de neur?nios individuais, assim como na pot?ncia do potencial de campo e na rela??o entre sua fase e os padr?es de disparo produzidos pela popula??o. Al?m disso, as conex?es laterais inter-hemisf?ricas modulam estas vari?veis dependendo da estimula??o feita fora do CRF. Observamos tamb?m uma influ?ncia deste circuito lateral na coer?ncia entre potenciais de campo entre eletrodos distantes. Em conclus?o, nossos resultados d?o suporte ? ideia de um mecanismo complexo de segmenta??o figura-fundo atuando desde as ?reas visuais prim?rias em diferentes escalas de frequ?ncia. Esse mecanismo parece envolver grupos de neur?nios ativos sincronicamente e dependentes da fase do potencial de campo. Nossos resultados tamb?m s?o compat?veis com a hip?tese que conex?es laterais de longo alcance tamb?m fazem parte deste mecanismo / Since Hubel and Wiesel s pioneer finding a vast body of literature has accumulated describing neuronal responses in the primary visual cortex (V1) to different visual stimuli. These stimuli mainly consisted of moving bars, dots or gratings which served to explore the responses to basic visual features such as orientation, direction of motion or contrast, among others, within a classical receptive field (CRF). However, in the last two decades it became increasingly evident that the activity of V1 neurons can be modulated by stimulation outside their CRF. Thus, early visual areas might be already involved in more complex visual tasks like, for example, the segmentation of an object or a figure from its (back)-ground. It is assumed that intrinsic long-range horizontal connections within V1 as well as feedback connections from higher visual areas are actively involved in the figure-ground segmentation process. Their possible role has been inferred from the analysis of the spike rate variations induced by stimuli placed outside the CRF of single neurons. Although it is very likely that those connections also have an impact on the joined activity of neurons involved in processing the figure and on their local field potentials (LFP), these issues remain understudied. In order to examine the context-dependent modulation of those activities, we recorded spikes and LFPs in parallel from up to 48 electrodes in the primary visual cortex of anesthetized cats. We stimulated with composite grating and natural scene stimuli focusing on populations of neurons whose CRFs were situated on the foreground figure. In addition, in order to examine the influence of horizontal connections we removed the inter-hemispheric input of the isotopic contralateral visual areas by means of reversible cooling deactivation. We did so because i) the intrinsic horizontal connections cannot be easily manipulated without directly affecting the measured signals, ii) because inter-hemispheric connections share the major anatomical features with the intrinsic lateral network and can be seen as a functional continuation of the latter across the two hemispheres and iii) because cooling causally and reversibly deactivates input connections by temporarily silencing the sending neurons and thus enables direct conclusions on their contribution. Our results demonstrate that the figure-ground segmentation mechanism is reflected in the spike rate of single neurons, as well as in their LFP power and its phase-relationship to the spike patterns produced by the population. In addition "lateral" inter-hemispheric connections modulate spike rates and LFP power depending on the stimulation of the neurons CRF surround. Further, we observe an influence of this lateral circuit on field- field coherences between remote recording sites. In conclusion, our findings support the idea of complex figure-ground segmentation mechanism acting already in early visual areas on different time scales. This mechanism seems to involve groups of neurons firing synchronously and dependent on the LFP s phase. Our results are also compatible with the hypothesis that long-range lateral connections contribute to that mechanism

O córtex visual desempenha papel essencial no processamento de informação visual. A primeira região do córtex a receber estímulos visuais é o córtex visual primário (V1) e pode ser subdividida anatomicamente em seis camadas, onde cada camada contém diferentes tipos e números de neurônios. Entender a forma como a informação é processada entre as diferentes camadas envolve o estudo da dinâmica dos padrões coletivos de atividade neural quando a rede é exposta a diferentes situações e como esses padrões relacionam-se com a organização estrutural e funcional da rede cortical. Essa dinâmica é afetada por mecanismos de plasticidade sináptica, de maneira que modelos computacionais que busquem capturá-la devem incluir tais mecanismos. Neste trabalho foi construído um modelo computacional de uma rede neural com 4000 neurônios baseada em informações sobre a estrutura local das conexões em V1 disponíveis na literatura neurobiológica. O modelo contém características estruturais consideradas fundamentais tais como: proporção entre neurônios inibitórios e excitatórios e probabilidades de conexões entre neurônios de diferentes populações em diferentes camadas. Os neurônios foram descritos pelo modelo de Izhikevich, reproduzindo três classes eletrofisiológicas mais abundantes no córtex: neurônios de disparo regular, para os excitatórios; neurônios de disparo rápido e baixo limiar de disparo, para os inibitórios. A regra de plasticidade sináptica utilizada foi do tipo plasticidade dependente dos tempos dos disparos neuronais (STDP em inglês), que pode fortalecer ou enfraquecer a força da conexão entre dois neurônios dependendo dos instantes dos seus disparos. Foram utilizadas versões diferentes dessa regra de plasticidade para sinapses excitatórias (STDPe) e inibitórias (STDPi). Foram simuladas situações com e sem plasticidade e alterando o tipo de neurônio inibitório presente na rede. Para cada uma, três protocolos de estimulação da rede foram utilizados: 1 estimulação por trens de disparos poissonianos aplicada a neurônios da camada 4 (simulando entradas talâmicas) e aplicada aleatoriamente aos neurônios da rede como ruído de fundo; 2 - pulsos aplicados a neurônios da camada 4 simulando estimulação visual com barras luminosas com diferentes orientações angulares; 3 - similar ao segundo protocolo, porém, estimulando a rede com dois pulsos alternantes de diferentes ângulos. Os parâmetros do modelo foram ajustados para que a atividade neural tivesse baixas frequências de disparos coerentes com dados experimentais. Esse ajuste foi mais fácil nos casos em que os neurônios inibitórios eram do tipo FS e havia STDPi. Os resultados mostraram que, de modo geral, os neurônios do tipo LTS contribuem para a formação de atividade síncrona na rede e este efeito foi amplificado com a STDPe. Para todos os protocolos, a STDPe aumentou a frequência média de disparos da rede e, para o segundo experimento, apesar da seletividade à orientação dos neurônios não ter sido alterada significativamente, houve mudanças visíveis na formação de assembleias funcionais. A competição da atividade dos neurônios no experimento 3 na presença da STDPe foi intensificada fortalecendo respostas funcionais de neurônios que não respondiam a ambos os estímulos. O balanço entre os dois tipos de regra de STDP manteve o equilíbrio entre as forças das conexões excitatórias e inibitórias. / The visual cortex plays essential role in the processing of visual information. The first region of the cortex that receives visual stimuli is the primary visual cortex (V1) or striate cortex, which can be anatomically divided into six layers, where each layer has different types and numbers of neurons. Understanding the way in which information is processed by the different layers involves the study of the dynamics of collective patterns of neural activity when the network is exposed to different situations, and how these patterns are related with the structural and functional organization of cortical network. This dynamics is affected by mechanisms of synaptic plasticity, so computational models which seek to capture it should include them. In this project a computational model of a neural network was built with 4000 neurons based on information on local connectivity in V1 from the neurobiological literature. The model has realistic structural characteristics such as the proportion between inhibitory and excitatory neurons and the connection probabilities among neurons from different populations of different layers. Neurons were described by the Izhikevich model, reproducing the three most abundant electrophysiological classes in cortex: RS, for the excitatory ones; FS and LTS, for the inhibitory neurons. The synaptic plasticity rule used was spike-timing dependent plasticity (STDP), whereby the synaptic strength between two neurons can increase or decrease depending on the timing of their spikes. Were used different versions of this plasticity rule to synapses made by excitatory neurons (STDPe) and by inhibitory neurons (STDPi). Different scenarios were simulated with and without plasticity and changing the type of inhibitory neuron present in the network. For each configuration, three network stimulation protocols were used: 1 - stimulation applied to layer 4 neurons (simulating thalamic inputs) modeled by Poissonian spike trains and background noise applied to all network neurons modeled in a similar manner; 2 - pulses applied to layer 4 neurons simulating visual stimulation with light bars at different angular directions; 3 - similar to the second protocol, however, stimulating the network with two alternating pulses of different angles. The parameters of the model were adjusted so that neural activity had low spike frequencies consistent with experimental data. This adjustment was easier in cases where inhibitory neurons were of FS type and had STDPi. The results showed that, in general, LTS neurons contribute to the formation of synchronous activity in the network and this effect was amplified with the insertion of STDPe. For all protocols, the STDPe increased the average firing frequency of the network. For Experiment 2, although the orientation selectivity of the neurons did not change significantly, there have been noticeable changes in the formation of functional assemblies. The competition of the activity of neurons in Experiment 3 in the presence of STDPe strengthened functional responses of neurons that do not respond to both stimuli. The balance between the two types of STDP rule maintained the equilibrium between excitatory and inhibitory connections.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-08-18T12:54:46Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Antonio Jorge Fontenele Neto.pdf: 9942923 bytes, checksum: 9de5bf466a9fc72acbc6a2a2d3a9c57c (MD5) / Made available in DSpace on 2016-08-18T12:54:46Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Antonio Jorge Fontenele Neto.pdf: 9942923 bytes, checksum: 9de5bf466a9fc72acbc6a2a2d3a9c57c (MD5) Previous issue date: 2015-08-25 / CAPEs / O córtex visual primário (V1) é a região do córtex cerebral responsável pela primeira etapa de processamento da informação visual capturada pela retina. Por ser uma das áreas corticais melhor compreendidas, V1 constitui um dos principais paradigmas de compreensão do processamento sensorial. Desde os anos 70 há uma extensa literatura que estuda propriedades de resposta de neurônios de V1, principalmente com eletrodos individuais e utilizando-se como modelo animal gatos e macacos. Tem-se conhecimento de onde partem seus principais inputs e quais estímulos fazem os neurônios dispararem (grades senoidais com determinadas frequências espaciais e temporais). Mais recentemente, com o uso de matrizes de eletrodos, se tornou possível a investigação de propriedades coletivas da atividade e codificação neurais, que não eram possíveis de serem desvendadas com eletrodos individuais. Além disso, no estado da arte tecnológico atual, o uso do rato como modelo animal permite o registro da atividade neural com os animais em comportamento livre (sem anestesia ou contenção). No entanto, pouco se sabe sobre especificidades das propriedades de resposta dos neurônios do córtex visual do rato. Este trabalho teve por objetivo desenvolver um aparato e um protocolo experimental no Laboratório de Neurociência de Sistemas e Computacional adequado para estudo das propriedades de resposta de neurônios de V1 de ratos usando matrizes de eletrodos. Finalmente, apresentamos resultados experimentais onde caracterizamos respostas de neurônios de V1 a diferentes estímulos visuais (Funções de Gabor ou Grades) seja em ruído denso ou rarefeito, variando as propriedades de frequências temporal e espacial de estimulação, densidades de estímulos, velocidade, etc. Concluímos que implementamos com sucesso a técnica experimental, que abre inúmeras perspectivas futuras de pesquisas nesta linha no Departamento de Física da Universidade Federal de Pernambuco. / The primary visual cortex (V1) is the cerebral cortex region responsible for the first processing step of the visual information captured by the retina. Being one of the most studied and well described cortical sensory areas, V1 is one of the main paradigms for the study of sensory processing. Since the 70s, there is a vast literature that studies properties of V1’s neurons, specially using single electrodes and using cats and monkeys as animal models. The anatomical conectivity of the visual pathway is known, from the retina to the lateral geniculate nucleus to V1, as well as the main visual stimulations that make V1 neurons fire (sinusoidal gratings with certain spatial and temporal frequencies). More recently, using multielectrode arrays, it became possible to study coletive properties of the activity and neural codification, that could not be unveiled with single electrodes. Furthermore with, the current state of the art in multielectrode recordings it is possible to record the neural activity in frelly behaving rats (without anesthesia or restraint). This represents an advantage in using the rat as animal model. However, little is known about specificities of the V1 neurons response properties in the rat. The aim of this work is to develop, in the Laboratório de Neurociência de Sistemas e Computacional, an apparatus and an experimental protocol suitable for the study of visual response properties of V1’s neurons in rats, using multielectrode array recordings. Finally, we present experimental results that characterize the response of V1’s neurons with different visual stimuli (Gabor or Grating Functions), either in dense os sparse noise modes, varying the spatial and temporal stimulation frequencies, stimulus density, speed, etc. We conclude that the experimental technique was implemented successfully. These results open important perspectives of future research on this field for the Departamento de Física at the Universidade Federal de Pernambuco.