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

Abstract

Systems consolidation, essential for long-term memory formation, orchestrates the reorganization of newly encoded memories from the cortex 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 the optokinetic reflex, 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. Optogenetic modulation of PC-IE post-learning uncovered a critical temporal window for its role in systems consolidation. Specifically, increasing PC-IE within 90 minutes after learning disrupted memory consolidation, while outside this window, memory retention remained unaffected. Under physiological conditions, PC-IE naturally decreased during this time frame and returned to baseline thereafter. Moreover, abnormally heightened PC-IE eliminated intrinsic plasticity in flocculus-targeting neurons (FTNs) within the medial vestibular nucleus (MVN), a key downstream circuit involved in long-term memory storage. These findings highlight the precise temporal dynamics of IE as a pivotal mechanism in systems consolidation, emphasizing its vulnerability to disruptions.