Venous cerebral blood volume increase during voluntary locomotion reflects cardiovascular changes

Abstract

Understanding how changes in the cardiovascular system contribute to cerebral blood flow (CBF) and volume (CBV) increases is critical for interpreting hemodynamic signals. Here we investigated how systemic cardiovascular changes affect the cortical hemodynamic response during voluntary locomotion. In the mouse, voluntary locomotion drives an increase in cortical CBF and arterial CBV that is localized to the forelimb/hindlimb representation in the somatosensory cortex, as well as a diffuse venous CBV increase. To determine if the heart rate increases that accompany locomotion contribute to locomotion-induced CBV and CBF increases, we occluded heart rate increases with the muscarinic cholinergic receptor antagonist glycopyrrolate, and reduced heart rate with the β1-adrenergic receptor antagonist atenolol. We quantified the effects of these cardiovascular manipulations on CBV and CBF dynamics by comparing the hemodynamic response functions (HRF) to locomotion across these conditions. Neither the CBF HRF nor the arterial component of the CBV HRF was significantly affected by pharmacological disruption of the heart rate. In contrast, the amplitude and spatial extent of the venous component of the CBV HRF was decreased by atenolol. These results suggest that the increase in venous CBV during locomotion was partially driven by peripheral cardiovascular changes, whereas CBF and arterial CBV increases associated with locomotion reflect central processes.

Time to wake up: Studying neurovascular coupling and brain-wide circuit function in the un-anesthetized animal

“…Mice rapidly (usually within one session) acclimate to head-fixation, and learn to ‘operate’ the treadmill. After acclimation, resting heart rates in head-fixed mice are comparable to those from recorded telemetrically from mice in their home cage (Gehrmann et al, 2000, Huo et al, 2015b) (Fig. 10), indicating that that head fixation after acclimation is not stressful.…”

“…10), indicating that that head fixation after acclimation is not stressful. In our hands, the pattern of evoked hemodynamic signals are stable up to 10 months of continuous imaging (Huo et al, 2015a, 2015b), which would not be the case if the animals were stressed. Many other groups have used head-fixed rodents, and have shown that they can perform complex, cognitively demanding tasks (Harvey et al, 2009; Komiyama et al, 2010; Mayrhofer et al, 2013; Mehta, 2007; Smear et al, 2011) that use memory or discrimination of stimuli at very high levels, which would not be possible if the animals were excessively stressed.…”

“…In another two-photon imaging study, urethane blocked the dilation of veins (Drew et al, 2011). The lack of venous dilation under some anesthetic regimens is likely due to the reduced blood pressure caused by anesthesia, as decreasing blood pressure in the awake animal blocks the venous dilation (Huo et al, 2015b). Interestingly, there are examples of putative slow venous dilations being detected using MRI (Kim and Kim, 2010; Silva et al, 2007a), though in both cases low doses of anesthetics were used.…”

“…This habituation procedure and schedule is based on those used in neurophysiology experiments (Dombeck et al, 2007; Zagha et al, 2013). With a stable preparation, the noise in the intrinsic signal due to animal motion is negligible, as it is several orders of magnitude below the amplitude of the sensory-evoked response (Huo et al, 2014; 2015a; 2015b). Two-photon microscopy is sensitive to animal movement, but movement during voluntary locomotion are typically small enough to be corrected using motion correction software (Dombeck et al, 2007; Gao and Drew, 2016).…”

“…The arterial dilation is localized to the somatosensory and visual cortex (Fig. 10), with little arterial dilation seen in the frontal cortex (Huo et al, 2014, 2015a, 2015b, Gao and Drew, 2016). …”