Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca²⁺ recordings

Abstract

Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping.

Simultaneous GCaMP6-based fiber photometry and fMRI in rats

“…When comparing to previously used fluorescent chemical dyes (Schmid et al, 2016; Schulz et al, 2012), the utilization of GCaMP6 (Chen et al, 2013), a newly improved protein-based GECI, enabled repeated measurement of calcium and BOLD signals. In addition, as a GECI, GCaMP6 can be selectively expressed in a defined cell population, which allows neural activity with cell-type specificity to be measured.…”

“…Techniques of chemical dyes or genetically encoded optical indicators have been greatly expanded and improved in recent years, and have been extensively used to record calcium or voltage-sensitive signals (Weber and Helmchen, 2014). Notably, simultaneous fiber photometry and fMRI has been successfully demonstrated in rats (Schmid et al, 2016; Schulz et al, 2012). Fiber photometry records an optical signal from a neuronal population through an optical fiber chronically implanted in the animal.…”

“…Such a simple setup makes it particularly suitable for use inside MRI scanners, as it requires minimal space and does not involve any metal components. By utilizing chemical dyes (OGB-1, Rhod-2 and Fluo-4) as calcium indicators, two studies simultaneously recorded the calcium signal, which directly reflects spiking activity, and fMRI data in animals (Schmid et al, 2016; Schulz et al, 2012). This novel method has opened a new avenue to investigating the neurovascular coupling relationship.…”

“…A previous study utilized chemical dyes (OGB-1, Rhod-2 and Fluo-4) as calcium indicators to simultaneously acquire calcium and BOLD signals in rats (Schulz et al, 2012), which showed robust activation of both signals in a forepaw stimulation paradigm. Another recent study employed a similar approach, with the neuronal activity modulated using optogenetics (Schmid et al, 2016). However, due to the nature of acute loading and decay of chemical dyes in brain tissue, it is difficult to conduct repeated and longitudinal experiments with chemical dyes.…”

Brain states govern the spatio-temporal dynamics of resting state functional connectivity

“…To provide direct evidence for this hypothesis, we conducted simultaneous optic-fiber based calcium recordings alongside fMRI measurements in slow wave state, as previously implemented 67 . When the component of down up transitions identified in the optical neural recordings were filtered out, we indeed found a decrease in correlation of cortical activity.…”