Differential modulation of positive and negative prediction errors by stimulus variability in the mouse posterior parietal cortex

To function in uncertain environments, we need to constantly update our internal model of the world. Sensory prediction errors are thought to drive these updates. EEG studies indicate that uncertainty affects neural correlates of prediction errors. It is unclear how uncertainty of the environment modulates prediction error responses in individual neurons. Here, we exposed awake head-restrained mice to sounds followed by tactile stimuli that were either fixed or variable in intensity, making them more or less predictable. Using tactile stimuli that were stronger or weaker than expected, we identified positive and negative prediction error neurons in layer 2/3 of the posterior parietal cortex with 2-photon calcium imaging. We show that positive prediction errors are upregulated while negative prediction errors are downregulated by variability. Finally, through modelling we show that variability-dependent modulation of inhibitory neurons best fits the data, suggesting a previously unrecognized role for inhibition in encoding uncertainty prediction errors.