Thalamic dual control of sleep and wakefulness

Abstract

Slow waves (0.5-4 Hz) predominate in the cortical electroencephalogram during non-rapid eye movement (NREM) sleep in mammals. They reflect the synchronization of large neuronal ensembles alternating between active (UP) and quiescent (Down) states and propagating along the neocortex. The thalamic contribution to cortical UP states and sleep modulation remains unclear. Here we show that spontaneous firing of centromedial thalamus (CMT) neurons in mice is phase-advanced to global cortical UP states and NREM-wake transitions. Tonic optogenetic activation of CMT neurons induces NREM-wake transitions, whereas burst activation mimics UP states in the cingulate cortex and enhances brain-wide synchrony of cortical slow waves during sleep, through a relay in the anterodorsal thalamus. Finally, we demonstrate that CMT and anterodorsal thalamus relay neurons promote sleep recovery. These findings suggest that the tonic and/or burst firing pattern of CMT neurons can modulate brain-wide cortical activity during sleep and provides dual control of sleep-wake states.

Reassessing the validity of slow-wave dynamics as a proxy for NREM sleep homeostasis

“…Optogenetic silencing of CMT neurons ( Fig. 4E) was previously shown to increase NREMS δ power during SD recovery sleep in the cingulate cortex, which receives direct input from the CMT (Gent et al, 2018a). We found that during CMT inhibition this increase was specific to the δ2 band, leaving δ1 activity unaffected ( Fig.…”

“…It has become increasingly clear that thalamocortical crosstalk is an important contributor to the generation of both the SO and δ-waves (Crunelli et al, 2015, Neske, 2015. For instance, cortical UP-states synchronize thalamic δoscillations (Steriade et al, 1991), which might contribute to the prominent nesting we observed of δ2-waves at δ1 onset, while excitatory thalamocortical input to the cortex can trigger cortical UP-state initiation and removing thalamic input reduces cortical SO period and synchrony (David et al, 2013, Lemieux et al, 2014, Gent et al, 2018a. Moreover, thalamic neurons are intrinsically capable of generating rhythmic oscillations at <1Hz frequencies (Blethyn et al, 2006, Crunelli et al, 2018, Fernandez et al, 2018, Halasz et al, 2014, Herrera et al, 2016 that could aid the strengthening of the cortical SO.…”

“…To gain insight into the underlying circuitry, we probed deeper cortical and sub-cortical layers (thalamus), using a published dataset (Gent et al, 2018a) of local field potential (LFP) tetrode recordings at 3 cortical [Visual (V2), Barrel, and Cingulate cortices] and 2 thalamic sites [centromedial thalamus (CMT), anterodorsal nucleus (AD)], at varying depths. Following a 4h SD ending at ZT4, high levels in both δ1-and δ2-power were observed, in visually similar patterns to cortical surface electrodes and strikingly similar across recording sites ( Fig.…”

“…In an effort to determine a thalamic contribution to either SW population, we optogenetically inhibited the centromedial thalamus (CMT), a non-sensory thalamic nucleus that we found to be important in the timing and manifestation of NREMS cortical SWs (Gent et al, 2018a). CMT inhibition boosted δ2 activity specifically, leaving δ1 in the cingulate cortex unaffected.…”

“…CMT inhibition boosted δ2 activity specifically, leaving δ1 in the cingulate cortex unaffected. Whether the δ2 augmentation is of thalamic or cortical origin is unclear as we quantified SWs during NREMS episodes consecutive to those during which the CMT was optogenetically silenced, indicating that increases in δ2 activity might be a cortical rebound phenomenon as SWs were suppressed during preceding optogenetic silencing (Gent et al, 2018a).…”