iScience. 2025 Nov 21. 28(11): 113760
Systems consolidation reorganizes newly encoded memories from cortical networks into downstream circuits. Although synaptic mechanisms are extensively characterized, the role of neuronal intrinsic excitability (IE) in this process remains relatively unexplored. Here, we utilized a cerebellum-dependent learning model to investigate the causal link between neuronal IE and memory consolidation. The optogenetic manipulation of Purkinje cells (PCs), the sole output of the cerebellar cortex, identified a crucial 90-min post-learning window during which PC-IE undergoes transient depression. Disrupting this decline by elevating PC-IE hindered long-term memory, whereas interventions outside this window did not. Elevated PC-IE spared basal ocular reflexes, indicating its role is specific to adaptive consolidation states. Moreover, increased PC-IE abolished learning-induced intrinsic plasticity in flocculus-targeting neurons (FTNs) of the medial vestibular nucleus (MVN), a downstream locus for persisting memory storage. These findings underscore the precise temporal dynamics of IE as a critical mechanism in systems consolidation, emphasizing its vulnerability to disruptions.
Keywords: Behavioral neuroscience; Neuroscience; Sensory neuroscience