Self-supervised predictive learning accounts for cortical layer-specificity

The neocortex constructs an internal representation of the world, but the underlying circuitry and computational principles remain unclear. Inspired by self-supervised learning algorithms, we propose a computational theory in which layer 2/3 (L2/3) integrates past sensory input, relayed via layer 4, with top-down context to predict incoming sensory stimuli. Learning is self-supervised by comparing L2/3 predictions with the latent representations of actual sensory input arriving at L5. We demonstrate that our model accurately predicts sensory information in context-dependent temporal tasks, and that its predictions are robust to noisy and occluded sensory input. Additionally, our model generates layer-specific sparsity, consistent with experimental observations. Next, using a sensorimotor task, we show that the model's L2/3 and L5 prediction errors mirror mismatch responses observed in awake, behaving mice. Finally, through manipulations, we offer testable predictions to unveil the computational roles of various cortical features. In summary, our findings suggest that the multi-layered neocortex empowers the brain with self-supervised predictive learning.