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Oxidative neuroenergetics in event-related paradigms.

ABSTRACT: Energetic basis of neural activity provides a solid foundation for noninvasive neuroimaging with calibrated functional magnetic resonance imaging (fMRI). Calculating dynamic changes in cerebral oxidative energy utilization (CMR(O(2))) is limited by uncertainties about whether or not the conventional blood oxygenation level-dependent (BOLD) model can be applied transiently using multimodal measurements of blood flow (CBF) and volume (CBV) that affect the BOLD signal. A prerequisite for dynamic calibrated fMRI is testing the linearity of multimodal signals within a temporal regimen, as assessed by signal strength (i.e., both intensity and width). If each hyperemic component (BOLD, CBV, CBF) is demonstrated to be linear with neural activity under various experimental conditions, then the respective transfer functions generated by deconvolution with neural activity should be time invariant and thus could potentially be used for calculating CMR(O(2)) transients. Hyperemic components were investigated at 11.7 T in alpha-chloralose-anesthetized rats and combined with electrophysiological recordings of local field potential (LFP) and multiunit activity (MUA) from the cortex during forepaw stimulation, in which stimulus number and frequency were varied. Although relationships between neural activity and stimulus features ranged from linear to nonlinear, associations between hyperemic components and neural activity were linear. Specific to each hyperemic component, a universal transfer function (with LFP or MUA) yielded predictions in agreement with experimental measurements. The results identified a component of the BOLD signal that can be attributed to significant changes in CMR(O(2)), even for temporal events separated by <200 ms.

SUBMITTER: Sanganahalli BG

PROVIDER: S-EPMC2760964 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Oxidative neuroenergetics in event-related paradigms.

Sanganahalli Basavaraju G BG Herman Peter P Blumenfeld Hal H Hyder Fahmeed F

The Journal of neuroscience : the official journal of the Society for Neuroscience 20090201 6

Energetic basis of neural activity provides a solid foundation for noninvasive neuroimaging with calibrated functional magnetic resonance imaging (fMRI). Calculating dynamic changes in cerebral oxidative energy utilization (CMR(O(2))) is limited by uncertainties about whether or not the conventional blood oxygenation level-dependent (BOLD) model can be applied transiently using multimodal measurements of blood flow (CBF) and volume (CBV) that affect the BOLD signal. A prerequisite for dynamic ca ...[more]

PMID: 19211878

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Project description:G protein coupled receptors (GPCRs) were first characterized as signal transducers that elicit downstream effects through modulation of guanine (G) nucleotide-binding proteins. The pharmacotherapeutic exploitation of this signaling paradigm has created a drug-based field covering nearly 50% of the current pharmacopeia. Since the groundbreaking discoveries of the late 1990s to the present day, it is now clear however that GPCRs can also generate productive signaling cascades through the modulation of ?-arrestin functionality. ?-Arrestins were first thought to only regulate receptor desensitization and internalization - exemplified by the action of visual arrestin with respect to rhodopsin desensitization. Nearly 20 years ago, it was found that rather than controlling GPCR signal termination, productive ?-arrestin dependent GPCR signaling paradigms were highly dependent on multi-protein complex formation and generated long-lasting cellular effects, in contrast to G protein signaling which is transient and functions through soluble second messenger systems. ?-Arrestin signaling was then first shown to activate mitogen activated protein kinase signaling in a G protein-independent manner and eventually initiate protein transcription - thus controlling expression patterns of downstream proteins. While the possibility of developing ?-arrestin biased or functionally selective ligands is now being investigated, no additional research has been performed on its possible contextual specificity in treating age-related disorders. The ability of ?-arrestin-dependent signaling to control complex and multidimensional protein expression patterns makes this therapeutic strategy feasible, as treating complex age-related disorders will likely require therapeutics that can exert network-level efficacy profiles. It is our understanding that therapeutically targeting G protein-independent effectors such as ?-arrestin will aid in the development of precision medicines with tailored efficacy profiles for disease/age-specific contextualities.

Dataset Information

Oxidative neuroenergetics in event-related paradigms.

Publications

Oxidative neuroenergetics in event-related paradigms.

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