Figure 5. Loss of Mef2c increases sleep need and decreases its resolution.

(A) SWA power (normalized to average SWA power over 24 hr) declines over the light phase as shown in a Mef2c^f/f mouse. (B) The decline is less apparent in an example from a Mef2c-cKO^Camk2a-Cre mouse. (C) Pooled data (Mef2c^f/f, n = 6; Mef2c-cKO^Camk2a-Cre, n = 11; C57BL/6, n = 6) SWA power decay over the light phase for WT (BL/6), Mef2c^f/f and Mef2c-cKO^Camk2a-Cre. (D) The average waking SWA power in 24 hr is similar for Mef2c-cKO^Camk2a-Cre and Mef2c^f/f and is used as a normalizing factor to assess averaged SWS episode power. (E) SWS-SWA power over time from an average of SWS episodes aligned from the time of transition from waking to SWS, set to t = 0. The time constant of decay, τ = 8.4 min, was calculated by best fit of the decay of power for the Mef2c^f/f but the decay fit was indeterminate for Mef2c-cKO^Camk2a-Cre (see Materials and methods section for details). By setting τ = 8.4 min, a best fit to single exponential decay provided a plateau value (minimal value), an extrapolated peak value and an indication of goodness of fit in comparison to Mef2c^f/f. The SWS-SWA power for Mef2c-cKO^Camk2a-Cre mice is greater than Mef2c^f/f as determined by the plateau value (Plt) and the peak value. The quality of the fit is reduced as indicated by the R² value. (F) The average SWS-SWA power of each genotype following repeated, regular bouts of 4 hr SD, was significantly increased compared to SWS-SWA power under baseline conditions. Mef2c-cKO^Camk2a-Cre mice failed to show this rebound response to sleep loss. (G) The time course of rebound across the 8 × 4 hr SD periods indicates that the lack of rebound in Mef2c-cKO^Camk2a-Cre is particularly prominent during the dark phase.

Figure 5—figure supplement 1. Loss of Mef2c does not influence sleep/waking time, but modestly alters spectral power distribution across states.

(A) A cumulative histogram of SWS episode durations shows a shift to the right for Mef2c^f/f from CS to SD condition indicative of increased need for sleep. For Mef2c-cKO^Camk2a-Cre the SD induced rightward shift is occluded, suggesting high sleep need in CS condition. (B) Time in waking, SWS, and REM (right axis) as a percent of total time is unchanged by loss of Mef2c. (C) Spectral power distribution is modulated by loss of MEF2C function. During waking, relative power in Mef2c-cKO^Camk2a-Cre mice is shifted to the slower delta range frequencies compared to Mef2c^f/f mice; during SWS, power in the delta range is decreased with loss of MEF2C function; during REM the power distribution is unaffected by genotype. Significant group by frequency differences are indicated by * for Mef2c^f/f and Mef2c-cKO^Camk2a-Cre groups.