Essential Thalamic Contribution to Slow Waves of Natural Sleep

Abstract

Slow waves represent one of the prominent EEG signatures of non-rapid eye movement (non-REM) sleep and are thought to play an important role in the cellular and network plasticity that occurs during this behavioral state. These slow waves of natural sleep are currently considered to be exclusively generated by intrinsic and synaptic mechanisms within neocortical territories, although a role for the thalamus in this key physiological rhythm has been suggested but never demonstrated. Combining neuronal ensemble recordings, microdialysis, and optogenetics, here we show that the block of the thalamic output to the neocortex markedly (up to 50%) decreases the frequency of slow waves recorded during non-REM sleep in freely moving, naturally sleeping-waking rats. A smaller volume of thalamic inactivation than during sleep is required for observing similar effects on EEG slow waves recorded during anesthesia, a condition in which both bursts and single action potentials of thalamocortical neurons are almost exclusively dependent on T-type calcium channels. Thalamic inactivation more strongly reduces spindles than slow waves during both anesthesia and natural sleep. Moreover, selective excitation of thalamocortical neurons strongly entrains EEG slow waves in a narrow frequency band (0.75-1.5 Hz) only when thalamic T-type calcium channels are functionally active. These results demonstrate that the thalamus finely tunes the frequency of slow waves during non-REM sleep and anesthesia, and thus provide the first conclusive evidence that a dynamic interplay of the neocortical and thalamic oscillators of slow waves is required for the full expression of this key physiological EEG rhythm.

Anatomical localization of Cav3.1 calcium channels and electrophysiological effects of T-type calcium channel blockade in the motor thalamus of MPTP-treated monkeys

“…However, because ML218 effects were found, regardless of the distance of the microinjections to the reticular nucleus (see Fig. 4), we believe that most of the changes described in our study were due to local drug effects in the basal ganglia-receiving territory of the thalamus (David et al 2013;Li et al 2005).…”

“…The identification of these was based on literature indicating that the mechanisms underlying the induction of LTS bursts lead to a progressive increment of the ISIs inside of the burst (see Fig. 5C3), referred to as the descelerando signature (David et al 2013). Bursts that failed to meet the criteria of rebound bursts were defined as non-rebound bursts.…”

Long-range projections coordinate distributed brain-wide neural activity with a specific spatiotemporal profile

“…However, recent evidence suggests that thalamic bursting plays a fundamental role in sensory processing (53,54). Studies of visual (55) and somatosensory (30,53) pathways demonstrate the presence of thalamic bursting in awake and attentive states, implying that bursting activity modulates sensory perception.…”

Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

“…Recordings in deafferented cortex show that slow oscillations can occur in the absence of thalamic connections (22). Yet basic functional anatomic and neurophysiological reasoning suggests that the thalamus is likely a significant participant in slow and δ oscillations (23,24). To address these questions in the context of induction and emergence from propofol anesthesia, we analyzed the coherence between the superficial layer (2/3, referred to as SL) and deep layers (5 and 6, referred to as DLs), layers of prelimbic cortex, and the different high-order thalamic nuclei (M, C, and S).…”

“…Electroencephalogram (EEG) recordings in humans during gradual induction of unconsciousness with propofol show the appearance of frontal β oscillations (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) at the onset of sedation, followed by the appearance of coherent frontal α (8-12 Hz) oscillations (7)(8)(9)(10) and widespread slow (0.1-1 Hz) and δ (1-4 Hz) oscillations (7,11,12) when subjects no longer respond to sensory stimuli. Biophysical models of neuronal dynamics have shown that whereas α and β oscillations can be generated by propofol's actions in cortex alone (13), coherent α oscillations require the participation of both thalamus and cortex (14).…”