Associative spine enlargement stabilizes wakefulness and enables goal-directed behaviors

Models of cognition often treat fast electrical dynamics as separate from slower associative plasticity. We asked whether rapid synaptic structural plasticity is required for coordinated cortical processing during wakefulness. We developed SynC, a chemogenetic perturbation that, upon A/C administration, reversibly blocks associative dendritic spine enlargement and impairs motor learning without detectably altering baseline synaptic/neuronal physiology. SynC activation in frontoparietal cortex reduced laser-dot chasing and delayed feeding initiation, and reduced wake-state stability. Population recordings revealed a locomotor-active but impaired regime with preserved mean activity and {gamma} power but reduced pairwise correlations during quiet, immobile epochs, with increased network dimensionality (Interm-C), intermittently interrupted by an arrest state (State-C) with suppressed {gamma} power. Thus, intact Rac1-dependent spine-enlargement mechanisms are acutely required to maintain the functional coupling necessary for coordinated cortical processing during wakefulness. One sentence summaryAcute, reversible in vivo blockade of associative spine enlargement shows that rapid structural plasticity is required to sustain cortical processing in EEG/EMG-defined waking.