Quantitative reconstruction of diverse circadian patterns in SANC FR under various conditions.

Abstract

(A) Averaged circadian HR fluctuations in anesthetized mice (BT = 37°C) with 12-h light cycles before (control; grey dashed line) and after SNA blockade (blue dashed line), PNA blockade (yellow dashed line), and ANS blockade (green dashed line) [38]. Circadian fluctuations were fitted using a sine function as described in [38] and normalized to HR at ZT6 with ANS blockade. (B) Simulated circadian FR patterns in a single mouse SANC (BT = 37°C; normalized to FR at ZT6 with ANS blockade) closely recapitulate experimental findings [38]. (C-D) Model simulations accurately reproduce minimal and maximal time-of-day FR (C), and normalized circadian amplitudes of FR (D) under control, SNA blockade, PNA blockade, and ANS blockade conditions. The normalized amplitude values are obtained by dividing circadian FR amplitudes in beats per minute (BPM) by the mean time-of-day FR. (E) Either additive or unidirectional modulation effects alone are insufficient to accurately reproduce time-of-day FRs under the control conditions. (F-G) Circadian rhythmicity of BT (36~38°C) enhances the circadian amplitude of FR under control conditions (grey dots) (F) with simulated Q10 = 2 in agreement with experimental studies (G) (15). (H-I) In aged model, simulated maximal FR reduction (25%; red dots) (H) is consistent with experimental findings (I) [25].</p