Abstract
Non-invasive investigation of physiological changes and metabolic events associated with brain activity in mice constitutes a major challenge. Conventionally, fMRI assesses neuronal activity by evaluating activity-evoked local changes in blood oxygenation levels (BOLD). In isoflurane-anaethetized mice, however, we found that BOLD signal changes during paw stimulation appear to be dominated by arousal responses even when using innocuous stimuli. Widespread responses involving both hemispheres have been observed in response to unilateral stimulation. MRS allows probing metabolic changes associated with neuronal activation and provides a complementary readout to BOLD fMRI for investigating brain activity. In this study we evaluated the sensitivity of a free induction decay (FID) based spectroscopic imaging (MRSI) protocol for the measurement of alterations in glutamate levels elicited by unilateral electrical paw stimulation at different current amplitudes. Coronal MRSI maps of glutamate distribution with 17 × 17 voxels of 1 µl volume have been recorded with a temporal resolution of 12 min. Significant region-specific increases in glutamate levels have been observed in the contralateral but not in the ispiateral S1 somatosensory cortex upon stimulation. The amplitude of glutamate changes increased in a dose-dependent manner with the stimulus amplitude. The study demonstrates feasibility of functional MRSI in mice for studying activity-evoked glutamate changes in a temporo-spatially resolved manner.
Highlights
Neural activity elicits a sequel of physiological and metabolic changes to account for the increased energy/oxygen demand by tissue
Neural activity is associated with increased neurotransmitter turnover and energy demand, i.e. adaptations in metabolic activity that are matched by local regulation of cerebral blood flow (CBF) and oxygen supply
A result of neurovascular coupling balancing oxygen delivery to and oxygen consumption by the tissue is the generation of BOLD contrast
Summary
Neural activity elicits a sequel of physiological and metabolic changes to account for the increased energy/oxygen demand by tissue. We found that in isoflurane-anesthetized mice quantification of changes in the BOLD fMRI signals elicited by sensory (e.g. electrical) paw stimulation was confounded by stimulus-induced alterations in cardiovascular parameters potentially associated with arousal[4,5,6] Such influences of systemic physiology on cerebral hemodynamic response may mask specific stimulus-elicited fMRI signals. BOLD fMRI responses were of widespread bilateral nature even though they were found to correlate with the stimulus amplitude It appears that activity measures based on neurotransmitter levels are less susceptible to systemic confounds than those based on neuro-vascular hemodynamic coupling and might reflect neural activity more intimately, at least when studying sensory stimulation in mice
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