Distributed cortical learning through LEC-mediated γ-synchrony

Despite the well-established theoretical and experimental foundations of dopamine-driven reinforcement learning, how the reward prediction error (RPE) teaching signal modifies specific cortical memory networks remains unclear. Neural oscillations are crucial for the temporal binding of activities across distributed cell ensembles. Here, we identify that mouse lateral entorhinal cortex layer 5 (LEC⁵) mediated intercortical γ-synchrony is a neural correlate of the RPE signal derived from dopamine neurons in the ventral tegmental area (VTA^DA). The VTA^DA-LEC⁵ circuit-based intercortical γ-synchrony facilitates both learning and memory retention, and at the single-cell level, entrains the activity of cortical latent Engrams. Human brain recordings also validate a role of γ-synchrony in the processing of prediction errors. These findings indicate that LEC⁵-mediated intercortical γ-synchrony functions as a reinforcement learning signal that facilitates the establishment of cortical memory networks.