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The 23rd Colloque Médecine et Recherche in the Neurosciences series of the Fondation Ipsen: "Micro-, meso- and macro-dynamics of the brain"Following on from last year's very successful Neurosciences Colloque Médecine et Recherche on the connectivity of the brain, this year's meeting focused on the dynamic interactions between the trillions of connections that produce the brain's extraordinarily complex functions. As with the studies of connectivity, the functional dynamics of the brain operates on scales ranging from the microscopic exchange at synapses, through the interplay in the circuits that underpin perception, memory, cognition, and decision-making to the properties of the system as a whole, the most challenging of which is consciousness. At this year's meeting, held in Paris on April 13th, leading researchers from Europe and the USA, including one of the recipients of the 2014 Nobel (News - Alert) Prize in Medicine or Physiology, will explore the latest results and thinking on the dynamics of the brain. This 23rd Colloque Médecine et Recherche in the Neurosciences series hosted by the Fondation IPSEN has been organised by György Buzsáki (Neuroscience Institute, New York University, New York, USA) and Yves Christen (Fondation IPSEN, Paris, France). The structural networks of connections between neurons provide the substrate for the brain's computational power but ultimately perception, memory, motor programming and consciousness all depend on the fluctuating tide of electrical and chemical signals in and between the neuronal networks. Huge technological advances in recording and imaging this activity are playing a crucial role in advancing our understanding of how these networks communicate and how they contribute to both normal and abnormal brain function. The signals can be probed and manipulated at all scales, ranging from recording from specific areas of single cells to determine how individual branches of a neuron solve behaviourally relevant computational problems (Michael Häusser, University College London, London, England) through multi-electrode recordings from neuronal assemblies or networks, to optogenetic and pharmacological interventions, and local and global imaging. An important advance is the adaption of these methods for use in awake animals, which has provided powerful access to neural activity during behaviour, revealing far more complexity than previously detected in anaesthetised animals. A good example of this is the work for which the 2014 Nobel Prize was awarded: the identification of so-called grid cells in the rat's hippocampus, a cortical structure involved in memory and spatial orientation (Edvard Moser, Centre for Neural Computation, Kavli Institute, Trondheim, Norway). Grid cells map the space around the animal using complex transformations that develop with experience to align the grid to the environment. Neurons in the primary visual cortex have classically been defined by their receptive fields, their responses to minimal components of the visual stimulus, such as lines or angles. Analysis on the levels of single cells and assemblies shows a far greater complexity: receptive fields are dynamically modulated by higher-level inputs as the natural environment changes (Yves Fregnac, CNRS, Gif-sur-Yvette, France). Similar dynamic contextual modulation is seen i rodents in the processing of information from the exquisitely sensitive whiskers. Making multiple electrode recordings in the strikingly organised fields in the somatosensory cortex that receive input from the whiskers while the animals use them to discriminate the size of a hole reveals a anticipatory signal from the motor cortex that modifies the response of the sensory input cells (Miguel Nicolelis, Duke University Medical Centre, Durham, USA). However, the complexity of the wiring in the six layers of the mammalian cortex is still proving difficult to analyse - the much simpler, three-layered cortex of the turtle is proving a useful model for examining information processing and circuit dynamics (Gilles Laurent, Max Planck Institute for Brain Research, Frankfurt, Germany). Decision-making is fundamental to all behaviours. Single- and multi-cell recordings combined with circuit imaging are being employed to examine the neural processing in hippocampus and cortex underlying the decisions a mouse makes while navigating a virtual environment (David Tank, Princeton University, USA). The decision-making process can be broken down into serial steps, with sensory processing preceding a motor planning anticipatory stage that requires short-term memory (Li Nuo, Janelia Farm Research Campus, Howard Hughes (News - Alert) Medical Research Institute, Ashburn, USA). But these complex computations do not depend only on the cortex: highly specialized loops between areas of the frontal cortex and the striatal areas deep in the midbrain are implicated in the decisions rodents make about the value (good or bad) of a stimulus; similar circuits are probably involved in human depression, anxiety and obsessive-compulsive behaviour (Ann Graybiel, Massachusetts Institute of Technology, Cambridge, USA). The participation of another midbrain structure, the thalamus, in hippocampal memory consolidation has been discovered in sophisticated experiments using brain activity to trigger regional and global functional magnetic resonance imaging (Nikos Logothetis, Max Planck Institute for Biological Cybernetics, Tübingen, Germany). Such work is providing a role for the oscillatory activity, a common feature of large-scale recordings such as electro-encephalograms, the function of which has long been disputed. Oscillatory activity is also a significant component of a two-stage model of memory consolidation that involves multiple hierarchical neuronal loops between neocortex and hippocampus; the model emphasises the importance of internal as well as external signals in these loops (Buzsáki). Conscious perception requires that cognitive tasks are broken down into a sequence of operations but only recently has it become feasible to correlate neural activity and specific mental content. Tracking conscious and unconscious stimuli in paradigms such as stimulus masking and in conditions such as blindsight (the residual, unconscious light perception seen in certain types of blindness) is enabling distributed asssemblies of neurons encoding current states of mind to be identified (Stanislas Dehaene, CEA/SAC/DSV/12BM, Gif-sur-Yvette, France). Integrated information theory may provide a structure for predicting what is needed for consciousness, an urgent requirement for working with subjects who cannot be interrogated, such as non-responsive patients in the clinic, newborn babies or animals very unlike ourselves (Giulio Tononi, University of Wisconsin, Madison, USA). The challenge of the brain's complexity is attracting large-scale research investment. The Allen Institute for Brain Science has already developed connectivity brain atlases for several species, including human, both adult and developing. A 10-year program established in 2012 is now concentrating on detailed analysis of mouse neocortex, with a focus on the loops between thalamus and cortex involved in visuo-motor behaviour, on scales ranging from synaptic ultrastructure and genetic transcription to the systems level, using a battery of experimental and modelling techniques (Christof Koch, Allen Institute for Brain Science, Seattle, USA). The European Human Brain Project is equally ambitious, aiming to build up information from the level of genes and proteins, through cell morphology to circuits, with the hope of ultimately understanding how new properties that lead to changes in behaviour can emerge from the activity of neurons embedded in networks and assemblies (Richard Frackowiak, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland). Another goal of this project is to evolve a theory for understanding the brain, with implications for better classification of brain diseases. About the Fondation Ipsen Established in 1983 under the aegis of the Fondation de France, the mission of the Fondation Ipsen is to contribute to the development and dissemination of scientific knowledge. The long-standing action of the Fondation Ipsen aims at fostering the interaction between researchers and clinical practitioners, which is indispensable due to the extreme specialization of these professions. The ambition of the Fondation Ipsen is to initiate a reflection about the major scientific issues of the forthcoming years. It has developed an important international network of scientific experts who meet regularly at meetings known as Colloques Médecine et Recherche, dedicated to six main themes: Alzheimer's disease, neurosciences, longevity, endocrinology, the vascular system and cancer science. Moreover the Fondation Ipsen has started since 2007 several meetings in partnership with the Salk Institute, the Karolinska Institutet, the Massachusetts General Hospital, the Days of Molecular Medicine Global Foundation as well as with the science journals Nature, Cell and Science. The Fondation Ipsen produced several hundred publications; more than 250 scientists and biomedical researchers have been awarded prizes and research grants. |
