In contrast, positive peaks in scalp EEG tightly corresponded to negative peaks of depth EEG and to ON periods with rigorous spiking, in accordance with a depolarized up state. We set out to examine

quantitatively the relationship between sleep slow waves and the underlying spiking activity across all brain regions where units were detected (Figure 3). Individual slow waves were detected automatically in the depth EEG of each brain region separately (e.g., cyan dots in Figure 2), and unit spiking activity surrounding slow waves was averaged. When focusing on the highest amplitude waves in each channel (top 20%), positive and negative peaks in depth EEG were associated with marked decreases and increases in unit discharges, respectively (Figures 3A and 3B; n = 600). This result should be viewed as a lower limit on the modulation strength, since timing variability across individual check details neurons introduced a temporal jitter, thereby smearing the average result. Therefore, the wave-triggered average of spiking activity was computed in each unit separately, searching for the minimal (maximal) rate while allowing for different time offsets around EEG peaks (n = 600, average of 10,595 waves per neuron). The minimal firing rate around EEG positivity was 39% ± 1% compared with the mean firing rate in NREM (N2+N3) sleep, and the mean latency of such OFF periods was 72 ± 9 ms before the positive

EEG peak. Around EEG negativity, a maximal firing rate of 198% ± 11% was found across individual units, at 46 ± 10 ms before the negative EEG peak. In each subject and in each brain region, individual neurons whose activity find more was highly modulated by slow waves were identified (Figure 3C). Such neurons were found not only in neocortex, but also in limbic structures such as hippocampus and amygdala. Given the variability across individual neurons, we examined the percentage of neurons showing significant phase locking to sleep slow waves separately in each brain structure (Figure S3;

see Experimental Procedures). The results revealed considerable variability (Figure 3D): the lowest percentages Florfenicol of phase locked neurons were found in anterior cingulate (12% ± 11%, n = 84 units in 11 regions, mean and SEM across electrodes). Neocortical regions (41% ± 11%, n = 109 units in 16 regions), hippocampus (49% ± 7%, n = 100 units in 17 regions), and parahippocampal gyrus (55% ± 10%, n = 97 units in 13 regions) showed intermediate effects, while the highest percentages of phase locked neurons were found in the amygdala (87% ± 11%, n = 61 units in 9 amygdala regions), entorhinal cortex (84% ± 13%, n = 67 units in 10 regions), and posterior cingulate cortex (100% ± 0%, n = 30 units in three regions). Since slow waves were detected in the depth EEG recorded ∼4 mm away from unit activity, the percentages of modulated neurons should be regarded as a lower bound.