Neuroscientists at the Sainsbury Wellcome Centre will watch specific groups of genetically-defined neurons fire in real time inside behaving animals, and then switch those neurons on and off to see what happens. This matters because the brain’s neural circuits are staggeringly complex. Until now, researchers could observe brain activity or behaviour, but could not prove that a particular pattern of neural firing *causes* a specific action, memory, or emotion. This project closes that gap by combining genetic tools, advanced microscopes, and precise neural manipulation to establish direct cause-and-effect links between circuit activity and behaviour. If successful, this fundamental science will produce a wiring diagram for how the brain computes—how it turns sensory input into movement, navigation, social interaction, and learning. That basic understanding is the foundation for tackling neurological and psychiatric disorders such as dementia, depression, and schizophrenia, which are among the most pressing health epidemics of our time. The work is primarily curiosity-driven, but past discoveries in fundamental neuroscience—from the squid giant axon to place cells—have repeatedly led to unexpected clinical breakthroughs.
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Neuroscience is entering a new and exciting period in which it will be possible to decipher the neural codes underlying cognition and emotion. Our aim is to position the Sainsbury Wellcome Centre at the heart of this development. The convergence of novel genetic, molecular, physiological, optical and behavioural approaches will enable scientists in the Sainsbury Wellcome Centre to monitor activity across genetically-defined ensembles of neurons in behaving animals, and to manipulate this activity in a temporally and spatially precise manner. This will make it possible for the first time to establish causal links between patterns of neural activity and behaviour, and to allow decisive tests of new theories about the computational properties of neural circuits. The new Centre will use model systems including rodents, and perhaps fish, and will maintain close contact with the fly research conducted at the Centre for Neural Circuits and Behaviour in Oxford. The animal models under consideration are excellent candidates for linking activity in neural circuits with well-defined behaviours. Drawing on current strengths at UCL and with the intention of maximizing collaborations with existing UCL neuroscientists, we envisage focusing on neural circuits underlying visual, motor, spatial, social and affective behaviours, during development and maturity, and for experience-dependent plastic changes. One advantage of such behaviours is that they can be studied across multiple species with different levels of complexity, allowing models with simpler nervous systems such as larva and adult zebrafish to facilitate conceptual development. They also provide a tractable methodological testbed before implementation in more complex systems (e.g. rodents). This blue sky research undertaken in the Centre will address some of the key problems in neuroscience and the basic understanding gained will have the additional benefit of providing the foundations for understanding neurological and psychiatric diseases which are emerging as some of the major epidemics of our time.
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