Thalamic Spindles Promote Memory Formation during Sleep through Triple Phase-Locking of Cortical, Thalamic, and Hippocampal Rhythms

While the interaction of the cardinal rhythms of non-rapid-eye-movement (NREM) sleep—the thalamo-cortical spindles, hippocampal ripples, and the cortical slow oscillations—is thought to be critical for memory consolidation during sleep, the role spindles play in this interaction is elusive. Combining optogenetics with a closed-loop stimulation approach in mice, we show here that only thalamic spindles induced in-phase with cortical slow oscillation up-states, but not out-of-phase-induced spindles, improve consolidation of hippocampus-dependent memory during sleep. Whereas optogenetically stimulated spindles were as efficient as spontaneous spindles in nesting hippocampal ripples within their excitable troughs, stimulation in-phase with the slow oscillation up-state increased spindle co-occurrence and frontal spindle-ripple co-occurrence, eventually resulting in increased triple coupling of slow oscillation-spindle-ripple events. In-phase optogenetic suppression of thalamic spindles impaired hippocampus-dependent memory. Our results suggest a causal role for thalamic sleep spindles in hippocampus-dependent memory consolidation, conveyed through triple coupling of slow oscillations, spindles, and ripples. Latchoumane et al. demonstrate a causal role of sleep spindles in memory formation. They show that optogenetic induction of thalamic spindles, when phase-locked to the slow oscillation up-state, enhances the triple coupling of slow oscillations-spindles-ripples together with hippocampus-dependent memory consolidation.