Abstract
One main limitation of established neuroimaging methods is the inability to directly visualize large-scale neural dynamics in whole mammalian brains at subsecond speeds. Optoacoustic imaging has advanced in recent years to provide unique advantages for real-time deep-tissue observations, which have been exploited for three-dimensional imaging of both cerebral hemodynamic parameters and direct calcium activity in rodents. Due to a lack of suitable calcium indicators excitable in the near-infrared window, optoacoustic imaging of neuronal activity at deep-seated areas of the mammalian brain has been impeded by the strong absorption of blood in the visible range of the light spectrum. To overcome this, we have developed and validated an intracardially perfused mouse brain preparation labelled with genetically encoded calcium indicator GCaMP6f that closely resembles in vivo conditions. By overcoming the limitations of hemoglobin-based light absorption, this new technique was used to observe stimulus-evoked calcium dynamics in the brain at penetration depths and spatio-temporal resolution scales not attainable with existing neuroimaging techniques.
Highlights
The mammalian brain is highly interconnected [1,2], comprised of specialized neuronal sub-circuits that link together into a larger, functional network [2]
To demonstrate the fundamental capacity for calcium imaging in deep regions of the rodent brain using functional OA neuro-tomography (FONT), we developed and validated here a GCaMP6f-expressing in situ mouse brain model intracardially perfused with artificial cerebrospinal fluid that overcomes the limitations of low penetration at visible wavelengths
The background absorption signal was clearly reduced when the blood was substituted by ACSF, enhancing the effective light penetration and the corresponding imaging depth
Summary
The mammalian brain is highly interconnected [1,2], comprised of specialized neuronal sub-circuits that link together into a larger, functional network [2]. Mapping neuronal activation with high spatio-temporal resolution across major portions of the intact brain, including deep and hard-to-access areas, has been one of the long-term goals of neuroscience, and could help discern its fundamental operating principles. To this end, an array of imaging techniques is in development to allow non-invasive investigation of the brain’s circuitry and network functionality. Among the established methods of functional whole-brain imaging, blood oxygen-level dependent functional magnetic resonance imaging (BOLD fMRI) is the most well-known. Cerebral hemodynamic changes are linked to neural activity via neurovascular coupling [4] and BOLD fMRI has been used
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