Cortical circuit activity underlying sleep slow oscillations and spindles

Abstract

Slow oscillations and sleep spindles are hallmarks of the EEG during slow-wave sleep (SWS). Both oscillatory events, especially when co-occurring in the constellation of spindles nesting in the slow oscillation upstate, are considered to support memory formation and underlying synaptic plasticity. The regulatory mechanisms of this function at the circuit level are poorly understood. Here, using two-photon imaging in mice, we relate EEG-recorded slow oscillations and spindles to calcium signals recorded from the soma of cortical putative pyramidal-like (Pyr) cells and neighboring parvalbumin-positive interneurons (PV-Ins) or somatostatin-positive interneurons (SOM-Ins). Pyr calcium activity was increased more than threefold when spindles co-occurred with slow oscillation upstates compared with slow oscillations or spindles occurring in isolation. Independent of whether or not a spindle was nested in the slow oscillation upstate, the slow oscillation downstate was preceded by enhanced calcium signal in SOM-Ins that vanished during the upstate, whereas spindles were associated with strongly increased PV-In calcium activity. Additional wide-field calcium imaging of Pyr cells confirmed the enhanced calcium activity and its widespread topography associated with spindles nested in slow oscillation upstates. In conclusion, when spindles are nested in slow oscillation upstates, maximum Pyr activity appears to concur with strong perisomatic inhibition of Pyr cells via PV-Ins and low dendritic inhibition via SOM-Ins (i.e., conditions that might optimize synaptic plasticity within local cortical circuits).

Posterior hippocampal spindle-ripples co-occur with neocortical theta-bursts and down-upstates, and phase-lock with parietal spindles during NREM sleep in humans

“…In humans, NC-SS (Hagler et al, 2018), and especially NC-SS/US increase firing (Csercsa et al, 2010;Mak-McCully et al, 2017;Gonzalez et al, 2018). In rodents, NC-SS (Seibt et al, 2017), and especially NC-SS/US (Niethard et al, 2018), are associated with strong Ca 2+ influx in NC pyramidal cell apical dendrites, and increased plasticity (Steriade and Timofeev, 2003). Behavioral consolidation in rodents depends on NC-SS/US coupling with HC-SWR (Maingret et al, 2016;Latchoumane et al, 2017).…”

Sleep spindles mediate hippocampal-neocortical coupling during sharp-wave ripples

“…Triggered by SOs, the thalamus generates sleep spindles, i.e., transient (0.5-2 s) oscillatory activity between [12][13][14][15][16] Hz, via thalamo-cortical loops [8]. Nested in SO up-states, spindles gate Ca 2+ influx into dendrites and promote synaptic plasticity [9][10][11]. Importantly, spindles have also been shown to group hippocampal sharp-wave ripples (SW-Rs) [12][13][14].…”

Spatiotemporal patterns of neocortical activity around hippocampal sharp-wave ripples

“…The main 636 diagonal of the ellipse was considered as the pupil diameter. 637Vigilance stages of each animal were classified as awake, NREM, and REM by thresholding 640 EMG and hippocampal theta-to-delta ratio signals(Niethard et al, 2018; Yang et al, 2014; 641 Yüzgeç et al, 2018b). Awake periods were identified by visual inspection of animal behavior 642 and EMG signal.…”