Sleep spindles are burstlike signals in the electroencephalogram (EEG) of the sleeping mammalian brain and electrical surface correlates of neuronal oscillations in thalamus. As one of the most inheritable sleep EEG signatures, sleep spindles probably reflect the strength and malleability of thalamocortical circuits that underlie individual cognitive profiles. We review the characteristics, organization, regulation, and origins of sleep spindles and their implication in non-rapid-eye-movement sleep (NREMS) and its functions, focusing on human and rodent. Spatially, sleep spindle-related neuronal activity appears on scales ranging from small thalamic circuits to functional cortical areas, and generates a cortical state favoring intracortical plasticity while limiting cortical output. Temporally, sleep spindles are discrete events, part of a continuous power band, and elements grouped on an infraslow time scale over which NREMS alternates between continuity and fragility. We synthesize diverse and seemingly unlinked functions of sleep spindles for sleep architecture, sensory processing, synaptic plasticity, memory formation, and cognitive abilities into a unifying sleep spindle concept, according to which sleep spindles 1) generate neural conditions of large-scale functional connectivity and plasticity that outlast their appearance as discrete EEG events, 2) appear preferentially in thalamic circuits engaged in learning and attention-based experience during wakefulness, and 3) enable a selective reactivation and routing of wake-instated neuronal traces between brain areas such as hippocampus and cortex. Their fine spatiotemporal organization reflects NREMS as a physiological state coordinated over brain and body and may indicate, if not anticipate and ultimately differentiate, pathologies in sleep and neurodevelopmental, -degenerative, and -psychiatric conditions.

Mammalian sleep alternates between sensory-responsive and protected offline periods via coordinated neural and cardiac rhythms.

We investigated the impact of thalamus on ongoing cortical activity in the awake, behaving mouse. We demonstrate that the desynchronized cortical state during active behavior is driven by a centrally generated increase in thalamic action potential firing, which can also be mimicked by optogenetic stimulation of the thalamus. The thalamus therefore is key in controlling cortical states.

Sleep affects brain activity globally, but many cortical sleep waves are spatially confined. Local rhythms serve cortical area-specific sleep needs and functions; however, mechanisms controlling locality are unclear. We identify the thalamic reticular nucleus (TRN) as a source for local, sensory-cortex-specific non-rapid-eye-movement sleep (NREMS) in mouse. Neurons in optogenetically identified sensory TRN sectors showed stronger repetitive burst discharge compared to non-sensory TRN cells due to higher activity of the low-threshold Ca2+ channel CaV3.3. Major NREMS rhythms in sensory but not non-sensory cortical areas were regulated in a CaV3.3-dependent manner. In particular, NREMS in somatosensory cortex was enriched in fast spindles, but switched to delta wave-dominated sleep when CaV3.3 channels were genetically eliminated or somatosensory TRN cells chemogenetically hyperpolarized. Our data indicate a previously unrecognized heterogeneity in a powerful forebrain oscillator that contributes to sensory-cortex-specific and dually regulated NREMS, enabling local sleep regulation according to use- and experience-dependence.

Highlights d In NREMS, thalamic noradrenaline (NA) levels are higher than in quiet wakefulness d Thalamic NA fluctuates over 50 s and is anticorrelated to sleep spindles d NA released from LC depolarizes thalamic neurons through a1and b-adrenoceptors d Infraslow LC activity coordinates heart-rate variations with spindles