CRCNS US-French Research Proposal: Neuronal circuit dynamics in zebrafish larvae: mechanisms, modulation, and mathematical modeling of network topology and attractor dynamics. Attractor neuronal circuits are recurrently connected networks whose temporal dynamics converge and settle to stable patterns. Theoretical attractor models have been used to explain a variety of cognitive functions and motor behaviour. Despite their importance for brain computations, a detailed description of physiological properties of these neuronal circuits is still missing; and the mechanisms underlying the emergence of attractor-like dynamics remain elusive. The Sumbre lab has recently shown that the optic tectum of the zebrafish larva is functionally organized according to neuronal assemblies (groups of highly correlated neurons). These assemblies exhibit all-or- none synergistic facilitation and competitive reciprocal inhibition generating single ?winners.? Both are features of attractor dynamics. In this project, the PIs will combine the experimental expertise of the Sumbre lab to monitor and analyze neuronal circuit dynamics in the zebrafish larva, and the mathematical skills of the Curto lab, applied to the theoretical investigation of attractor dynamics. More specifically, the Sumbre lab will use light-sheet microscopy and optogenetics (jGCaMP7f and reaChR) to monitor and manipulate the population activity of neuronal attractor circuits in the zebrafish larva. This approach will allow the detailed description of the physiological properties of neuronal attractor circuits (e.g. cell-type description, functional properties of all single neurons, etc.), and to investigate the modulation of the attractor dynamics by sensory experience and the internal state of the brain. The Curto lab will use topological data analysis (TDA) methods for the analysis of the acquired datasets to investigate higher-order correlations and the structure of functional connectivity within neuronal attractor circuits. In addition, mathematical modeling will reveal the neuronal mechanisms underlying the circuit?s attractor dynamics and the modulation of these dynamics. Principles learned from these theoretical approaches will then be tested experimentally in the Sumbre lab, using optogenetics. This multidisciplinary and complementary project will bring novel insights on the principles dictating the generation of neuronal attractor circuits and illuminate their functional role in the brain computations.
Understanding the dynamics of neural circuits is critical for studying their function and dysfunction across the nervous system. Many psychiatric diseases, such as schizophrenia and epilepsy, are thought to arise as a result of circuit-level changes that disrupt normal dynamics. Our research investigates the role of attractor dynamics in simple neural circuits, and studies how these dynamics are modulated by sensory experience and changes in internal state. This will provide an important step towards understanding neural circuit dynamics in both healthy and diseased networks.
