Increased cerebral activity suppresses baroreflex control of heart rate in freely moving mice

Abstract

We assessed whether increased cerebral activity suppressed baroreflex control of heart rate (HR) and, if so, whether this occurred prior to the onset of locomotion in daily activity of mice. We measured mean arterial pressure (MAP, arterial catheter), cerebral blood flow in the motor cortex (CBF, laser-Doppler flowmetry), and electroencephalogram in free-moving mice (n = 8) during 12 daytime hours. The contribution of baroreflex control of HR to MAP regulation was determined during a total resting period for approximately 8 h from the cross-correlation function (R(t)) between spontaneous changes in HR (HR) and MAP (MAP) every 4 s and the sensitivity was determined from HR/MAP where R(t) was significant (P < 0.05). The power density ratio of theta to delta wave band in electroencephalogram (theta/delta), determined every 4 s as an index of cerebral activity, was positively correlated with CBF during 73 +/- 3% of the total resting period (P < 0.05) and with R(t) during 59 +/- 2% (P < 0.05). When each measurement during the resting period was divided into seven bins according to the level of theta/delta, CBF was 91 +/- 2% in the lowest bin and 118 +/- 3% in the highest bin (P < 0.001), R(t) was 0.69 +/- 0.06 and 0.27 +/- 0.04 (P < 0.001) and HR/MAP (beats min(1) mmHg(1)) was 12.4 +/- 0.9 and 7.5 +/- 0.9 (P < 0.001), respectively, with significant correlations with theta/delta (all P < 0.002). Moreover, mice started to move in approximately 30 sec after the sequential increases of theta/delta and R(t), mice started to move at 5 times higher probability than after a given time, followed by a rapid increase in MAP by approximately 10 mmHg. These results suggest that increased cerebral activity suppresses baroreflex control of HR and this might be related to the start of voluntary locomotion with a rapid increase in MAP.

Figure 1

Schematic illustration of the implantation of electroencephalogram (EEG) electrodes and a stainless-steel pipe for cerebral blood flow (CBF) measurement

Figure 2. Typical example of measurements in a free-moving mouse

Top to bottom: activity counts, ratio of θ to δ wave band in EEG (θ/δ), CBF, cross-correlation function (R(t)) between ΔMAP and ΔHR, ΔHR/ΔMAP, HR and MAP in the mouse for 90 min. *R(t) was transformed to Z_R(t). θ/δ and Z_R(t) determined every 4 s were averaged for a period from t− 40 to t+ 40 s (21 values) while moving t by an increment of 4 s. These values were used to determine the correlation period with θ/δ (Table 1) and the probability of locomotion (Fig. 4B). The part with a filled bar is shown on a larger scale in Fig. 4A.

Figure 4. Cerebral activity, Z_R(t) and voluntary locomotion

A, typical example of activity counts, moving average of θ/δ, CBF and moving average of Z_R(t) on an expanded time scale from the part indicated by the filled bar in Fig. 2 (19.5–38.5 min). B, the probability of locomotion after a given time and after the increase in θ/δ and Z_R(t). Means and s.e.m. bars are presented for 8 mice. ***Significant difference from the value after a given time, P < 0.001.

Figure 3. CBF, Z_R(t), HR and MAP (A) and ΔHR/ΔMAP (B) in graded levels of θ/δ in free-moving mice

Means and s.e.m. bars are presented for 8 mice. Data in the resting period for ∼8 h in each mouse were used for analyses. ΔHR/ΔMAP was determined when R(t) between ΔHR and ΔMAP was significant regardless of negative or positive. Significant differences from values at 0–0.25 of θ/δ, *P < 0.05, **P < 0.01 and ***P < 0.001.

Figure 5. θ/δ, CBF, Z_R(t), HR and MAP (A), and ΔHR/ΔMAP and activity counts (B) before and after the onset of voluntary locomotion

Means and s.e.m. bars are presented for 8 mice. Analyses were performed on data that met 3 criteria: (1) both θ/δ and Z_R(t) increased to > threshold of 2 s.d. during the total resting period; (2) the increases were followed by locomotion within 30 s; and (3) locomotion lasted longer than 60 s. *Because some ΔHR/ΔMAP was lacking when R(t) was not significant, they were interpolated from the next values and means and s.e.m. for 8 mice were calculated as in other variables. **Means and s.e.m. of ΔHR/ΔMAP were calculated for 24 trials (3 trials × 8 mice) without interpolating the missing values. In this case, the number of slopes calculated is presented below the figure.