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

Neuron. 2017 Jul 19;95(2):424-435.e6. doi: 10.1016/j.neuron.2017.06.025. Epub 2017 Jul 6.

Abstract

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.

Keywords: NREM sleep; closed-loop optogenetic; contextual memory consolidation; hippocampus; prefrontal cortex; sharp wave-ripples; sleep spindles; slow oscillations; thalamic reticular nucleus.

MeSH terms

  • Animals
  • Electroencephalography / methods
  • Hippocampus / physiology*
  • Memory / physiology*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neocortex / physiology*
  • Optogenetics / methods
  • Sleep / physiology*
  • Thalamus / physiology*