title: Low-frequency calcium oscillations accompany deoxyhemoglobin oscillations in rat somatosensory cortex.
abstract: Spontaneous low-frequency oscillations (LFOs) of blood-oxygen-level-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 (HbO2) in both large blood vessels and capillaries. The HbR and HbO2 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 CBFV oscillations to hypercapnia, which triggers blood vessel vasodilation, suggests its dependence on vascular effects that are distinct from the LFOs detected in HbR, HbO2, 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).
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794; Congwu.Du@stonybrook.edu.
authors.forename: Congwu
authors.initials: C
authors.lastname: Du
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.affiliation: Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Koretsky
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794;
authors.forename: Yingtian
authors.initials: Y
authors.lastname: Pan
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D020013:Calcium Signaling; D002245:Carbon Dioxide / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology; D005453:Fluorescence; D006454:Hemoglobins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010108:Oxyhemoglobins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000378:metabolism*; D013997:Time Factors
chemical_list: D006454:Hemoglobins; D010108:Oxyhemoglobins; D002245:Carbon Dioxide; C100003:deoxyhemoglobin
keywords: cerebral hemodynamic; neuroimaging; neuronal calcium; resting-state functional connectivity; spontaneous low-frequency brain oscillations