Abstract
Neurovascular coupling describes the link between neuronal activity and cerebral blood flow. This relationship has been the subject of intense scrutiny, with most previous work seeking to understand temporal correlations that describe neurovascular coupling. However, to date, the study of spatial correlations has been limited to two-dimensional mapping of neuronal or vascular derived signals emanating from the brain’s surface, using optical imaging techniques. Here, we investigate spatial correlations of neurovascular coupling in three dimensions, by applying a single 10 ms pulse of light to trigger optogenetic activation of cortical neurons transduced to express channelrhodopsin2, with concurrent fMRI. We estimated the spatial extent of increased neuronal activity using a model that takes into the account the scattering and absorption of blue light in brain tissue together with the relative density of channelrhodopsin2 expression across cortical layers. This method allows precise modulation of the volume of activated tissue in the cerebral cortex with concurrent three-dimensional mapping of functional hyperemia. Single pulse opto-fMRI minimizes adaptation, avoids heating artefacts and enables confined recruitment of the neuronal activity. Using this novel method, we present evidence for direct proportionality of volumetric spatial neurovascular coupling in the cerebral cortex.
Highlights
The development of functional MRI technology has had the most profound impact on neuroscience and basic cognitive research
The time-course of the blood oxygen level dependent (BOLD) response triggered by a single 10 ms pulse of light shared some characteristics with those previously reported to be evoked by short sensory stimulations (Fig. 1e)
Following application of a single 10 ms light pulse there was a delay (~1 s) prior to a rapid increase in BOLD signal that returned to baseline within the following 8–10 s, similar to that previously reported in some event related studies
Summary
The development of functional MRI (fMRI) technology has had the most profound impact on neuroscience and basic cognitive research. An experimental approach widely used to study neurovascular coupling is to record correlations between measures of neuronal activity and that of brain hemodynamics. In this study the extent of optogenetically-induced increases in neuronal activity is estimated (and not measured) using earlier data that describe the scattering and absorption of blue light in brain tissue together with histological assessment of relative ChR2 expression in the cortex. Using this approach, we investigated correlations between the estimated volume of increased neuronal activity and the measured volume of the resultant functional hyperemic response. The methods and results presented here represent the first investigation of spatial neurovascular correlations in three dimensions
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