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

The last decade has seen a surge in the development of Brain-Machine Interfaces (BMI) as assistive neural devices for paralysis patients. Current BMI research typically involves a subject performing movements by controlling a robotic prosthesis. The neural signal that we consider for analysis is the Local Field Potential (LFP). The LFP is a low frequency neural signal recorded from intra-cortical electrodes, and has been recognized as one containing movement information. This thesis investigates hand-movement prediction using LFP data as input. In Chapter 1, we give an overview of Brain Machine Interfaces. In Chapter 2, we review the necessary concepts in time series analysis and pattern recognition. In the final chapter, we discuss classification accuracies when considering Summed power and Coherence as feature vectors.

abstract: The increasing availability of experimental data and computational power have resulted in increasingly detailed and sophisticated models of brain structures. Biophysically realistic models allow detailed investigations of the mechanisms that operate within those structures. In this work, published mouse experimental data were synthesized to develop an extensible, open-source platform for modeling the mouse main olfactory bulb and other brain regions. A “virtual slice” model of a main olfactory bulb glomerular column that includes detailed models of tufted, mitral, and granule cells was created to investigate the underlying mechanisms of a gamma frequency oscillation pattern (“gamma fingerprint”) often observed in rodent bulbar local field potential recordings. The gamma fingerprint was reproduced by the model and a mechanistic hypothesis to explain aspects of the fingerprint was developed. A series of computational experiments tested the hypothesis. The results demonstrate the importance of interactions between electrical synapses, principal cell synaptic input strength differences, and granule cell inhibition in the formation of the gamma fingerprint. The model, data, results, and reproduction materials are accessible at https://github.com/justasb/olfactorybulb. The discussion includes a detailed description of mechanisms underlying the gamma fingerprint and how the model predictions can be tested experimentally. In summary, the modeling platform can be extended to include other types of cells, mechanisms and brain regions and can be used to investigate a wide range of experimentally testable hypotheses. / Dissertation/Thesis / Doctoral Dissertation Neuroscience 2019

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第20881号 / 理博第4333号 / 新制||理||1622(附属図書館) / 京都大学大学院理学研究科数学・数理解析専攻 / (主査)准教授 梅田 亨, 教授 上 正明, 教授 雪江 明彦 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM

The hippocampal CA1 is crucial for myriad types of learning and memory. It is theorized to provide a spatiotemporal framework for the encoding of relevant information during learning, allowing an individual to create a cognitive map of its environment and experiences. To probe CA1 network dynamics that underlie such complex cognitive function, in this work we used recently developed cellular optical imaging techniques that provide high spatial and temporal resolutions. Genetically-encoded calcium indicators offer the ability to record intracellular calcium dynamics, a proxy of neural activity, from hundreds of cells in behaving animals with single cell resolution in genetically-defined cell types. In complement, recently developed genetically-encoded voltage indicators have enabled direct recording of transmembrane voltage of individual genetically-defined cells in behaving animals. The work presented here uses the genetically-encoded calcium indicator GCaMP6f and the genetically-encoded voltage indicator SomArchon to interrogate the activities of individual hippocampal CA1 neurons and their relationship to the dynamics of the broader network during behavior. First, we provide the first in vivo, real-time evidence that two unique populations of CA1 cells encode trace conditioning and extinction learning, two distinct phases of hippocampal-dependent learning. The population of cells responsible for the representation of extinction learning emerges within one session of extinction training. Second, we perform calcium imaging in a mouse model containing a total knockout of NEXMIF, a gene causative of autism spectrum disorder. We reveal that loss of NEXMIF causes over-synchronization of the CA1 circuit, particularly during locomotion, impairing the information encoding capacity of the network. Finally, we conduct voltage imaging of CA1 pyramidal cells and parvalbumin (PV)-positive interneurons, with simultaneous recording of local field potential (LFP), to characterize how cellular-level membrane dynamics and spiking relate to network-level LFP. We demonstrate that in PV neurons, membrane potential oscillations in the theta frequency range show consistent synchrony with LFP theta oscillations and organize spike timing of the PV population relative to LFP theta, indicating that PV interneurons orchestrate theta rhythmicity in the CA1 network. In summary, this dissertation utilizes genetically-encoded optical reporters of neural activity, providing critical insights into the function of the CA1 as a flexible, diverse network of individual neurons.

No description available.

Cette thèse a pour objectif de contribuer à la modélisation, à la simulation et à l’analyse des signaux contenant des potentiels d’action extracellulaires (EAPs), tels que mesurés in-vivo par des microélectrodes implantées dans le cerveau. Les modèles actuels pour la simulation des EAPs consistent soit en des modèles compartimentaux très détaillés et lourds en calcul, soit en des modèles dipolaires jugés trop simplistes. Dans un premier temps, une approche de simulation des EAPs se situant entre ces deux extrêmes est proposée, où la somme des contributions des compartiments du neurone est traitée comme une convolution, appliquée aux courants membranaires d’un seul compartiment actif. L'analyse des EAPs passe par une étape de classification des potentiels d'action détectés dans le signal enregistré, qui consiste à discriminer les formes de potentiels d’action et ainsi à identifier l'activité de neurones uniques. Dans cette thèse, une nouvelle approche basée sur l’inférence bayésienne est développée permettant l'extraction et la classification simultanées des EAPs. La méthode est appliquée à des signaux générés à l'aide de l'approche de simulation proposée plus haut, confirmant la qualité de la méthode de classification introduite et illustrant la capacité de la méthode de simulation à générer des EAPs réalistes de formes diverses et discriminables. Nous avons enrichi une modélisation de l’activité hippocampique réalisée dans l’équipe permettant de reproduire des oscillations dans ces bandes fréquentielles spécifiques en introduisant les EAPs, ceci afin d’évaluer les contributions de l'activité synaptique et celle des potentiels d’action à certaines bandes de fréquence des signaux enregistrés. Finalement, une étude sur signaux réels enregistrés dans le cadre de l'étude de la perception des visages chez l'homme a été menée, illustrant les performances de la méthode de spike sorting proposée dans un cadre réel et ouvrant la discussion sur les perspectives qu'offrent ces travaux de thèse pour l'étude de questions neuroscientifiques basées sur l'analyse de signaux multi-échelle. / The objective of this thesis is to contribute to the modelling, simulation and analysis of signals containing extracellular action potentials (EAPs), as measured in vivo by microelectrodes implanted in the brain. Current models for the EAPs simulation consist either of very detailed and computationally heavy compartmental models or dipole models considered too simplistic. An EAP simulation approach between these two extremes is proposed, where the sum of the contributions of the neuron compartments is treated as a convolution, applied to the membrane currents of a single active compartment. The analysis of EAPs involves a step of classifying the action potentials detected in the recorded signal, which consists in discriminating the forms of action potentials and thus identifying the activity of single neurons In this thesis, a new approach based on Bayesian inference is developed allowing the simultaneous extraction and classification of EAPs. The method is applied to signals generated using the simulation approach proposed above, confirming the quality of the sorting method introduced and illustrating the ability of the simulation method to generate realistic EAPs of various and discriminatory forms. We modified a model of hippocampal activity previously proposed in our team, able to reproduce oscillations in specific frequency bands, by including the EAPs model, which allowed to evaluate the contributions of synaptic activity and that of action potentials the recorded signals. Finally, a study on real signals recorded as part of the study of face perception in humans is conducted, illustrating the performance of the proposed spike sorting method in a real setting and opening the discussion on the perspectives offered by this thesis work for the study of neuroscientific questions based on multiscale signal analysis.

Infant vocalisations are uniquely salient sounds in the environment. They universally attract attention and compel the listener to respond with speed and care. They provide a wealth of information to parents about their infant’s needs and affective state. There is a scientific consensus that early parenting has a profound impact on child development. In particular, the sensitivity with which parents respond to their infant’s communicative cues has been shown to affect cognitive and socio-emotional outcomes. The mechanisms underlying such sensitivity are not well understood. In this thesis, adults’ sensitivity to infant cues will be considered in terms of two components, the ‘promptness’ and ‘appropriateness’ of responses, as originally conceptualised by Bell and Ainsworth (1972). Promptness of responses is considered in terms of adults’ ability to move with speed and effort after listening to infant vocalisations. Appropriateness, on the other hand, is considered in terms of adults’ ability to differentiate between functionally significant parameters in infant vocalisations. The effect of modifiable environmental factors on the promptness and appropriateness of responses is also investigated. Finally, a focused investigation of the brain basis of responses to infant vocalisations is presented. Overall, findings demonstrated that infant vocalisations undergo privileged, specialised processing in the adult brain. After hearing an infant cry, adults with and without depression were found to move with greater coordination and effort. Adults were also found to be attuned to subtle parameters in infant cries. This sensitivity was shown to be affected by two participant-level factors, depression and previous musical training. Furthermore, this sensitivity could be enhanced through intervention, as evidenced by findings from short-term, perceptual discrimination training. The notion of privileged processing of infant vocalisations is further supported by evidence of early discrimination of infant sounds in a survival-related subcortical brain structure. Future directions for this work include directly relating current experimental measures of adults’ responses to infant cues with parental sensitivity to infant communication during dynamic interactions. Translating current findings into applied settings would require an investigation of the effects of factors such as musical and perceptual training on sensitivity to infant cues in at-risk populations, such as mothers and fathers with depression. Lastly, an increased understanding of the brain basis of adults’ sensitivity to infant cues will provide insight into our greatest challenge: parenting our young.

The activity of networks subserving memory and learning in the hippocampus is under the control of GABAergic interneurons. In order to test the contribution of distinct cell types, I have recorded extracellularly, labelled, and identified different types of interneuron in area CA3 of the hippocampus, a region implicated in the generation of gamma and theta oscillations, and the initiation of sharp-waves. I present here a detailed analysis of the spike timing of parvalbumin-positive (PV) basket and physiologically identified pyramidal cells in area CA3, relative to various network states recorded in area CA3 and CA1 simultaneously. Additionally, I have shown by detailed analysis that five classes of previously recorded and identified CA1 interneuron fired with cell type specific firing patterns relative to local gamma oscillations. In CA3, PV basket cells fired phase locked to theta and gamma oscillations recorded in CA1 as well as in CA3, and increased their firing rates during CA1 sharp-waves. Pyramidal cells in CA3 were also phase-locked, but fired at phases different from basket cells. During theta oscillations, CA3 pyramidal and PV basket cells were phase locked to both CA1 and CA3 theta equally, suggesting a wide coherence of these oscillations; in contrast, cells fired more strongly phase-locked to gamma oscillations in CA3 than in CA1, suggesting a specific role for CA3 in the generation of this rhythm. In contrast to theta and gamma oscillations, CA3 basket cells were phase-locked to ripples in area CA3 but not in CA1. Overall, my results show that the spike timing of several types of interneuron in CA1, and PV basket cells in CA3, is correlated in a cell- and area-specific manner with the generation of particular states of synchronous activity.

The goal of this thesis is to investigate the functional role of the cortical column architecture within some of the existing brain coding theories. Here I focus on the hierarchical models of predictive coding and the 'phase of firing' coding hypothesis. Using an oddball paradigm consisting of a sequence of identical sounds interspersed with rare, unexpected sounds, one can observe a difference between the scalp potentials evoked by oddball and common sounds. This difference has been linked to predictive coding and novelty detection, and Stimulus Specific Adaptation (SSA) has been suggested as a likely substrate at the single neuron level. In order to simultaneously constrain hierarchical models of predictive coding, and so as to investigate the contributions that neural processing within the different cytoarchitectonic layers of the primary auditory cortex (A1) may make to SSA, I simultaneously recorded multi-unit activity and current source density (CSD) profiles across all layers in A1 of the rat in response to standard and oddball tones. Our results suggest that SSA arises at the level of the thalamocortical synapse and is further enhanced in the supragranular layers. The phase of low-frequency Local Field Potentials (LFPs) in primary sensory cortices carries stimulus related information and disambiguates the information about different stimuli evoking similar spike rates. However, it is yet unclear how these informative LFP phase values arise within the laminar organization of cortical columns. To address this issue, I performed CSD recordings in the area A1 of anaesthetized rats during the presentation of complex naturalistic sounds. Information theoretic analysis revealed that most LFP phase information originates from discrete CSD events consisting of strong granular-superficial-layer dipoles, likely triggered by bursts of thalamocortical activation. These events, which occur at rates of 2-4 Hz, reliably reset LFP phases at times of strong network excitation. They therefore provide a useful reference frame to measure neural activity with respect to salient times of stimulus history. CSD events display a diverse, stimulus-dependent morphology: these reflect the outcomes of cortical computations which result in varying extents of activation of infragranular output layers.