Low-frequency calcium oscillations accompany deoxyhemoglobin oscillations in rat somatosensory cortex

Abstract

Spontaneous low-frequency oscillations (LFOs) of blood-oxygenlevel-dependent (BOLD) signals are used to map brain functional connectivity with functional MRI, but their source is not well understood. Here we used optical imaging to assess whether LFOs from vascular signals covary with oscillatory intracellular calcium (Ca 2+ i ) and with local field potentials in the rat's somatosensory cortex. We observed that the frequency of Ca 2+ i oscillations in tissue (∼0.07 Hz) was similar to the LFOs of deoxyhemoglobin (HbR) and oxyhemoglobin (HbO 2 ) in both large blood vessels and capillaries. The HbR and HbO 2 fluctuations within tissue correlated with Ca 2+ i oscillations with a lag time of ∼5-6 s. The Ca 2+ i and hemoglobin oscillations were insensitive to hypercapnia. In contrast, cerebral-blood-flow velocity (CBFv) in arteries and veins fluctuated at a higher frequency (∼0.12 Hz) and was sensitive to hypercapnia. However, in parenchymal tissue, CBFv oscillated with peaks at both ∼0.06 Hz and ∼0.12 Hz. Although the higher-frequency CBFv oscillation (∼0.12 Hz) was decreased by hypercapnia, its lower-frequency component (∼0.06 Hz) was not. The sensitivity of the higher CBF V oscillations to hypercapnia, which triggers blood vessel vasodilation, suggests its dependence on vascular effects that are distinct from the LFOs detected in HbR, HbO 2 , Ca 2+ i , and the lower-frequency tissue CBFv, which were insensitive to hypercapnia. Hemodynamic LFOs correlated both with Ca 2+ i and neuronal firing (local field potentials), indicating that they directly reflect neuronal activity (perhaps also glial). These findings show that HbR fluctuations (basis of BOLD oscillations) are linked to oscillatory cellular activity and detectable throughout the vascular tree (arteries, capillaries, and veins).spontaneous low-frequency brain oscillations | resting-state functional connectivity | neuronal calcium | cerebral hemodynamic | neuroimaging M easures of resting-state functional connectivity with functional MRI (fMRI) are based on spontaneous low-frequency blood-oxygen-level-dependent (BOLD) oscillations that occur throughout the brain with the assumption that regions with correlated oscillations are functionally connected (1, 2). The networks that emerge from resting-state functional connectivity correspond roughly with neuroanatomical connectivity (3, 4) and are modified by brain diseases (5-7). BOLD signals in fMRI reflect the interplay between hemodynamics (including blood volume and velocity of blood flowing in the vessels) and cellular (neuronal and glial) metabolism, which affect the amount of deoxygenated hemoglobin (HbR) in brain tissue that leads to changes in BOLD fMRI (8,9). Human studies using near-infrared spectroscopy (NIRS) (10) have reported low-frequency oscillations (LFOs) of ∼0.04-0.1 Hz for oxygenated hemoglobin (HbO 2 ) and HbR in the brain consistent with those measured by BOLD (11). However, there is still no quantitative understanding of the relative direct contribution of spontaneous oscillations in cellular...

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