Cerebellar systems consolidation driven by the temporal dynamics of Purkinje cell excitability

Abstract

AbstractSystems consolidation, essential for long-term memory formation, orchestrates the reorganization of newly encoded memories into subsequent neural circuitry. While the role of synaptic mechanism in consolidation is well understood, the contribution of neuronal intrinsic excitability (IE) remains relatively unexplored. Herein, we adopted a cerebellum-dependent learning model, and manipulated IE of the sole output of the cerebellar cortex, Purkinje cells (PCs), to corroborate the direct causality between neuronal IE and memory consolidation and assessed its impact on intrinsic plasticity of the downstream neural circuits. Optogenetic excitation disrupted consolidation but was effective only within the 90 min post-learning time window. Notably, PC-IE temporarily weakened, but the effect faded beyond 90 minutes. Furthermore, abnormally increased PC-IE abolished intrinsic plasticity in flocculus-targeting neurons, a post-circuitry of cortical PCs, within the medial vestibular nucleus. These findings thus emphasize the precise temporal dynamics of IE, highlighting it as a crucial mechanism for systems consolidation.