Information processing in visual systems

One of the goals of neuroscience is to understand how animals perceive sensory information. This thesis focuses on visual systems, to unravel how neuronal structures process aspects of the visual environment. To characterise the receptive field of a neuron, we developed spike-triggered independent component analysis. Alongside characterising the receptive field of a neuron, this method provides an insight into its underlying network structure. When applied to recordings from the H1 neuron of blowflies, it accurately recovered the sub-structure of the neuron. This sub-structure was studied further by recording H1's response to plaid stimuli. Based on the response, H1 can be classified as a component cell. We then fitted an anatomically inspired model to the response, and found the critical component to explain H1's response to be a sigmoid non-linearity at output of elementary movement detectors. The simpler blowfly visual system can help us understand elementary sensory information processing mechanisms. How does the more complex mammalian cortex implement these principles in its network? To study this, we used multi-electrode arrays to characterise the receptive field properties of neurons in the visual cortex of anaesthetised mice. Based on these recordings, we estimated the cortical limits on the performance of a visual task; the behavioural performance observed by Prusky and Douglas (2004) is within these limits. Our recordings were carried out in anaesthetised animals. During anaesthesia, cortical UP states are considered "fragments of wakefulness" and from simultaneous whole-cell and extracellular recordings, we found these states to be revealed in the phase of local field potentials. This finding was used to develop a method of detecting cortical state based on extracellular recordings, which allows us to explore information processing during different cortical states. Across this thesis, we have developed, tested and applied methods that help improve our understanding of information processing in visual systems

Segregation of cortical head direction cell assemblies on alternating theta cycles

High-level cortical systems for spatial navigation, including entorhinal grid cells, critically depend on input from the head direction system. We examined spiking rhythms and modes of synchrony between neurons participating in head direction networks for evidence of internal processing, independent of direct sensory drive, which may be important for grid cell function. We found that head direction networks of rats were segregated into at least two populations of neurons firing on alternate theta cycles (theta cycle skipping) with fixed synchronous or anti-synchronous relationships. Pairs of anti-synchronous theta cycle skipping neurons exhibited larger differences in head direction tuning, with a minimum difference of 40 degrees of head direction. Septal inactivation preserved the head direction signal, but eliminated theta cycle skipping of head direction cells and grid cell spatial periodicity. We propose that internal mechanisms underlying cycle skipping in head direction networks may be critical for downstream spatial computation by grid cells.We kindly thank S. Gillet, J. Hinman, E. Newman and L. Ewell for their invaluable consultations and comments on previous versions of this manuscript, as well as M. Connerney, S. Eriksson, C. Libby and T. Ware for technical assistance and behavioral training. This work was supported by grants from the National Institute of Mental Health (R01 MH60013 and MH61492) and the Office of Naval Research Multidisciplinary University Research Initiative (N00014-10-1-0936). (R01 MH60013 - National Institute of Mental Health; MH61492 - National Institute of Mental Health; N00014-10-1-0936 - Office of Naval Research Multidisciplinary University Research Initiative)Accepted manuscrip

SIMONE: a realistic neural network simulator to reproduce MEA-based recordings

International audienceContemporary multielectrode arrays (MEAs) used to record extracellular activity from neural tissues can deliver data at rates on the order of 100 Mbps. Such rates require efficient data compression and/or preprocessing algorithms implemented on an application specific integrated circuit (ASIC) close to the MEA. We present SIMONE (Statistical sIMulation Of Neuronal networks Engine), a versatile simulation tool whose parameters can be either fixed or defined by a probability distribution. We validated our tool by simulating data recorded from the first olfactory relay of an insect. Different key aspects make this tool suitable for testing the robustness and accuracy of neural signal processing algorithms (such as the detection, alignment, and classification of spikes). For instance, most of the parameters can be defined by a probabilistic distribution, then tens of simulations may be obtained from the same scenario. This is especially useful when validating the robustness of the processing algorithm. Moreover, the number of active cells and the exact firing activity of each one of them is perfectly known, which provides an easy way to test accuracy

Interneuron NMDA receptor ablation induces hippocampus-prefrontal cortex functional hypoconnectivity after adolescence in a mouse model of schizophrenia

Although the etiology of schizophrenia is still unknown, it is accepted to be a neurodevelopmental disorder that results from the interaction of genetic vulnerabilities and environmental insults. Although schizophrenia’s pathophysiology is still unclear, postmortem studies point toward a dysfunction of cortical interneurons as a central element. It has been suggested that alterations in parvalbumin-positive interneurons in schizophrenia are the consequence of a deficient signaling through NMDARs. Animal studies demonstrated that early postnatal ablation of the NMDAR in corticolimbic interneurons induces neurobiochemical, physiological, behavioral, and epidemiological phenotypes related to schizophrenia. Notably, the behavioral abnormalities emerge only after animals complete their maturation during adolescence and are absent if the NMDAR is deleted during adulthood. This suggests that interneuron dysfunction must interact with development to impact on behavior. Here, we assess in vivo how an early NMDAR ablation in corticolimbic interneurons impacts on mPFC and ventral hippocampus functional connectivity before and after adolescence. In juvenile male mice, NMDAR ablation results in several pathophysiological traits, including increased cortical activity and decreased entrainment to local gamma and distal hippocampal theta rhythms. In addition, adult male KO mice showed reduced ventral hippocampus-mPFC-evoked potentials and an augmented low-frequency stimulation LTD of the pathway, suggesting that there is a functional disconnection between both structures in adult KO mice. Our results demonstrate that early genetic abnormalities in interneurons can interact with postnatal development during adolescence, triggering pathophysiological mechanisms related to schizophrenia that exceed those caused by NMDAR interneuron hypofunction alone.Fil: Alvarez, Rodrigo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Pafundo, Diego Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Zold, Camila Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Belforte, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin