Cooperative thalamocortical circuit mechanism for sensory prediction errors

The brain functions as a prediction machine, utilizing an internal model of the world to anticipate sensations and the outcomes of our actions. Discrepancies between expected and actual events, referred to as prediction errors, are leveraged to update the internal model and guide our attention towards unexpected events1-10. Despite the importance of prediction error signals for various neural computations across multiple brain regions, surprisingly little is known about the neural circuit mechanisms responsible for their implementation. Here we describe a thalamocortical disinhibitory circuit required for generating sensory prediction errors in mouse primary visual cortex (V1). Using calcium imaging with optogenetic manipulations as mice traverse a familiar virtual environment, we show that violation of animals predictions by an unexpected visual stimulus preferentially boosts responses of layer 2/3 V1 neurons most selective for that stimulus. Prediction errors specifically amplify the unexpected visual input, rather than representing a non-specific surprise or difference signal about how the visual input deviates from animals predictions. Selective amplification of unexpected visual input is implemented by a cooperative mechanism requiring thalamic input from the pulvinar, and cortical vasoactive-intestinal-peptide-expressing (VIP) inhibitory interneurons. In response to prediction errors, VIP neurons inhibit a specific subpopulation of somatostatin-expressing (SOM) inhibitory interneurons that gate excitatory pulvinar input to V1, resulting in specific pulvinar-driven response-amplification of the most stimulus-selective neurons in V1. Therefore, the brain prioritizes unpredicted sensory information by selectively increasing the salience of unpredicted sensory features through the synergistic interaction of thalamic input and neocortical disinhibitory circuits.