This paper integrates several levels of description - from the synaptic, through systems modelling, to behaviour. Gurney, K.N., Humphries, M.D., Redgrave, P., 2015. A New Framework for Cortico-Striatal Plasticity: Behavioural Theory Meets In Vitro Data at the Reinforcement-Action Interface. PLoS biology 13, e1002034. doi:10.1371/journal.pbio.1002034 Operant learning requires that reinforcement signals interact with action representations at a suitable neural interface. Much evidence suggests that this occurs when phasic dopamine, acting as a reinforcement prediction error, gates plasticity at cortico-striatal synapses, and thereby changes the future likelihood of selecting the action(s) coded by striatal neurons. But this hypothesis faces serious challenges. First, cortico-striatal plasticity is inexplicably complex, depending on spike timing, dopamine level, and dopamine receptor type. Second, there is a credit assignment problem—action selection signals occur long before the consequent dopamine reinforcement signal. Third, the two types of striatal output neuron have apparently opposite effects on action selection. Whether these factors rule out the interface hypothesis and how they interact to produce reinforcement learning is unknown. We present a computational framework that addresses these challenges. We first predict the expected activity changes over an operant task for both types of action-coding striatal neuron, and show they co-operate to promote action selection in learning and compete to promote action suppression in extinction. Separately, we derive a complete model of dopamine and spike-timing dependent cortico-striatal plasticity from in vitro data. We then show this model produces the predicted activity changes necessary for learning and extinction in an operant task, a remarkable convergence of a bottom-up data-driven plasticity model with the top-down behavioural requirements of learning theory. Moreover, we show the complex dependencies of cortico-striatal plasticity are not only sufficient but necessary for learning and extinction. Validating the model, we show it can account for behavioural data describing extinction, renewal, and reacquisition, and replicate in vitro experimental data on cortico-striatal plasticity. By bridging the levels between the single synapse and behaviour, our model shows how striatum acts as the action-reinforcement interface. -- Kevin Gurney, PhD, FSB Professor of Computational Neuroscience Adaptive Behaviour Research Group Department of Psychology, University of Sheffield, S10 2TP, UK <http://www.shef.ac.uk/%7Eabrg/> http://abrg.group.shef.ac.uk/people/kevin/ ------------- "Email is a wonderful thing for people whose role in life is to be on top of things. But not for me; my role is to [get to] the bottom of things. What I do takes long hours of studying and uninterruptible concentration." Donald Knuth: Professor Emeritus of the Art of Computer Programming at Stanford University, and winner of the 1974 Turing Award.