Global and local fMRI signals driven by neurons defined optogenetically by type and wiring

Abstract

Despite a rapidly-growing scientific and clinical brain imaging literature based on functional MRI using blood oxygenation level dependent (BOLD)1 signals, it remains controversial if BOLD signals in a particular region can be caused by activation of local excitatory neurons2. This difficult question is central to the interpretation and utility of BOLD, with major significance for fMRI studies in basic research and clinical applications3. Using a novel integrated technology unifying optogenetic4–13 control of inputs with high-field fMRI signal readouts, we show here that specific stimulation of local CaMKIIα-expressing excitatory neurons, either in neocortex or thalamus, elicits positive BOLD signals at the stimulus location with classical kinetics. We also show that optogenetic fMRI (ofMRI) allows visualization of the causal effects of specific cell types defined not only by genetic identity and cell body location, but also by axonal projection target. Finally, we show that ofMRI within the living and intact mammalian brain reveals BOLD signals in downstream targets distant from the stimulus, indicating that this approach can be used to map the global effects of controlling a local cell population. In this respect, unlike both conventional fMRI studies based on correlations14 and fMRI with electrical stimulation which will also directly drive afferent and nearby axons, this ofMRI approach provides causal information about the global circuits recruited by defined local neuronal activity patterns. Together these findings provide an empirical foundation for the widely-employed fMRI BOLD signal, and the features of ofMRI define a potent tool that may be suitable for functional circuit analysis as well as global phenotyping of dysfunctional circuitry.

Neurocomputational account of how the human brain decides when to have a break

“…This complex neural signal with precise spatiotemporal characteristics was identified with both fMRI and MEG using standard analytical tools, which validates the usual assumptions about the relationships between electromagnetic and hemodynamic activity (18)(19)(20)(21)(22). Due to its high temporal resolution, MEG brought evidence that the electromagnetic activity emitted by our regions of interest indeed followed the neural dynamics that was modeled and convolved with hemodynamic response to fit fMRI data.…”

Long-range projections coordinate distributed brain-wide neural activity with a specific spatiotemporal profile

“…Upon completion of all fMRI and electrophysiological recording experiments, a selected number of animals (n = 3 for VPM; n = 2 for POm) were transcardially perfused, and their brains sectioned and prepared. Consecutive sections (120 μm apart) were prepared according to a previously published procedure (78). Double or triple immunofluorescence was assessed using a confocal scanning laser microscope.…”

Low-frequency hippocampal–cortical activity drives brain-wide resting-state functional MRI connectivity

“…Because the DG primarily receives cortical terminal projections and acts as a bridge for corticohippocampal-cortical network communication, we examined how spatiotemporally specific activity initiated in the dorsal DG (dDG) influences cortical activity and subsequent brain-wide rsfMRI connectivity by combining optogenetic, cell-specific stimulation of Ca 2+ /calmodulindependent protein kinase IIa (CaMKIIα)-expressing excitatory neurons (i.e., dDG granule cells) and large-scale fMRI detection (35)(36)(37)(38). We also examined the functional effects of such changes in brain-wide rsfMRI connectivity on sensory processing.…”