Abstract
.SignificanceAlthough emerging evidence suggests that the hemodynamic response function (HRF) can vary by brain region and species, a single, canonical, human-based HRF is widely used in animal studies. Therefore, the development of flexible, accessible, brain-region specific HRF calculation approaches is paramount as hemodynamic animal studies become increasingly popular.AimTo establish an fMRI-compatible, spectral, fiber-photometry platform for HRF calculation and validation in any rat brain region.ApproachWe used our platform to simultaneously measure (a) neuronal activity via genetically encoded calcium indicators (GCaMP6f), (b) local cerebral blood volume (CBV) from intravenous Rhodamine B dye, and (c) whole brain CBV via fMRI with the Feraheme contrast agent. Empirical HRFs were calculated with GCaMP6f and Rhodamine B recordings from rat brain regions during resting-state and task-based paradigms.ResultsWe calculated empirical HRFs for the rat primary somatosensory, anterior cingulate, prelimbic, retrosplenial, and anterior insular cortical areas. Each HRF was faster and narrower than the canonical HRF and no significant difference was observed between these cortical regions. When used in general linear model analyses of corresponding fMRI data, the empirical HRFs showed better detection performance than the canonical HRF.ConclusionsOur findings demonstrate the viability and utility of fiber-photometry-based HRF calculations. This platform is readily scalable to multiple simultaneous recording sites, and adaptable to study transfer functions between stimulation events, neuronal activity, neurotransmitter release, and hemodynamic responses.
Highlights
Our interpretation of functional MRI data is built on the assumption that neuronal and vascular responses are tightly coupled.[1,2] The process by which changes in local neural activity lead to changes in cerebral blood flow (CBF) and blood volume[3] is often termed neurovascular coupling and this relationship can be described mathematically with a hemodynamic response function (HRF)
We use the spectral peak photon count as the unit shown in Figs. 1(d)–1(f) because it can be monitored in real time during the preparation for photometry-cerebral blood volume (CBV) recording
We provide an example of a HRF derived from spontaneous GCaMP6f and photometry-CBV signals in the prelimbic cortex (PrL), where the targeted site was 3.5-mm deep from brain surface in rats [Figs. 6(a) and 6(b)]
Summary
Our interpretation of functional MRI data is built on the assumption that neuronal and vascular responses are tightly coupled.[1,2] The process by which changes in local neural activity lead to changes in cerebral blood flow (CBF) and blood volume[3] is often termed neurovascular coupling and this relationship can be described mathematically with a hemodynamic response function (HRF). FMRI studies typically assigned a single canonical human HRF across brain regions (hereafter as canonical HRF), derived from two gamma functions.[4] emerging evidence shows that neurovascular coupling can be substantially different between species, brain regions, and physiological conditions.[5,6,7,8,9,10] use of the canonical HRF could lead to inaccurate interpretation of fMRI data, especially in preclinical studies that often utilize anesthetized non-human species. Some recent fMRI studies have adapted to use empirically derived
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