Abstract
Our knowledge of the brain has evolved over millennia in philosophical, experimental and theoretical phases. We suggest that the next phase is simulation neuroscience. The main drivers of simulation neuroscience are big data generated at multiple levels of brain organization and the need to integrate these data to trace the causal chain of interactions within and across all these levels. Simulation neuroscience is currently the only methodology for systematically approaching the multiscale brain. In this review, we attempt to reconstruct the deep historical paths leading to simulation neuroscience, from the first observations of the nerve cell to modern efforts to digitally reconstruct and simulate the brain. Neuroscience began with the identification of the neuron as the fundamental unit of brain structure and function and has evolved towards understanding the role of each cell type in the brain, how brain cells are connected to each other, and how the seemingly infinite networks they form give rise to the vast diversity of brain functions. Neuronal mapping is evolving from subjective descriptions of cell types towards objective classes, subclasses and types. Connectivity mapping is evolving from loose topographic maps between brain regions towards dense anatomical and physiological maps of connections between individual genetically distinct neurons. Functional mapping is evolving from psychological and behavioral stereotypes towards a map of behaviors emerging from structural and functional connectomes. We show how industrialization of neuroscience and the resulting large disconnected datasets are generating demand for integrative neuroscience, how the scale of neuronal and connectivity maps is driving digital atlasing and digital reconstruction to piece together the multiple levels of brain organization, and how the complexity of the interactions between molecules, neurons, microcircuits and brain regions is driving brain simulation to understand the interactions in the multiscale brain.
Highlights
Our knowledge of the brain has evolved over millennia in philosophical, experimental and theoretical phases
The main drivers of simulation neuroscience are big data generated at multiple levels of brain organization and the need to integrate these data to trace the causal chain of interactions within and across all these levels
We show how industrialization of neuroscience and the resulting large disconnected datasets are generating demand for integrative neuroscience, how the scale of neuronal and connectivity maps is driving digital atlasing and digital reconstruction to piece together the multiple levels of brain organization, and how the complexity of the interactions between molecules, neurons, microcircuits and brain regions is driving brain simulation to understand the interactions in the multiscale brain
Summary
Brain research evolved through a series of fundamental transformations of human thinking to approach the mind and the brain. Since neither a comprehensive repertory of data nor a complete map of the brain exists or will likely be obtained purely from experiments, we obviously cannot do this blindly It requires building the digital copy by formulating principles of cellular structure to synthesize all the neurons and glial cells, principles of molecular organization and interaction, principles of how ion channels and receptors are formed and distributed in neurons, principles of synaptic connectivity, principles of how brain regions are connected, and principles of how the brain is coupled to the body. It is through formulating and exercising these principles that simulation neuroscience makes progress systematic and understanding tractable. To explore the origin and making of this paradigm shift, we reconstruct the deep historical paths leading to simulation neuroscience through the philosophical, experimental and theoretical phases of brain research, in particular, from the first observations of the nerve cell to modern attempts to digitally reconstruct and simulate the brain, by identifying the major scientific, technological and conceptual breakthroughs that have guided this passionate quest of humans to understand the brain and their own condition
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