A reactivated thalamocortical plasticity window promotes learning and is reshaped by experience

Abstract

Adult sensory loss can reactivate critical-period-like thalamocortical plasticity, but whether this reactivation defines a temporally gated circuit state that facilitates learning and is reciprocally shaped by experience remains unknown. Here we define its in vivo trajectory and functional consequences in adult mouse barrel cortex. Infraorbital nerve transection opened a transient window of enhanced layer 4 thalamocortical gain. Training during this window lowered whisker-detection thresholds and promoted learning by accelerating the transition to stable performance. Local GluN2B blockade prevented both cortical potentiation and the learning advantage, linking critical-period-associated plasticity mechanisms to adaptive behavior in the adult brain. Neuropixels recordings showed that weak inputs preferentially increased neuronal responses, whereas strong inputs produced sharper temporal coding. The relationship was reciprocal: experience reshaped the trajectory of this circuit state, with training before the normal peak advancing the emergence of potentiation, training during the active window prolonging the potentiated state, and training after closure failing to reinstate potentiation. State prolongation accompanied more persistent sensory memory. These findings establish a reciprocal, timing-dependent interaction between endogenous plasticity and experience, revealing a general principle by which adult circuits can convert transient plastic potential into adaptive behavioral change and informing strategies that align training with periods of heightened plasticity.