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

By Jin Hyung Lee, R. Durand, Viviana Gradinaru, Feng Zhang, I. Goshen, Dae-Shik Kim, Lief Ericsson Fenno, Charu Ramakrishnan, Karl Deisseroth. Nature, 2010

703 citations recorded by the source corpus.

Despite a rapidly-growing scientific and clinical brain imaging literature based on functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) signals, it remains controversial whether BOLD signals in a particular region can be caused by activation of local excitatory neurons. This difficult question is central to the interpretation and utility of BOLD, with major significance for fMRI studies in basic research and clinical applications. Using a novel integrated technology unifying optogenetic control of inputs with high-field fMRI signal readouts, we show here that specific stimulation of local CaMKIIα-expressing excitatory neurons, either in the 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 correlations and fMRI with electrical stimulation that 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-used 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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/7ecdddfd92933b41bc2d9e659d63cfbfa315152e

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Citations in the corpus

Structural foundations of resting-state and task-based functional connectivity in the human brain (2013, background): “Cogn Affect Behav Neurosci 4(2):117–126.”
Brain graphs: graphical models of the human brain connectome. (2011, background): “The anatomical and physiological significance of structural and functional MRI signals has been extensively debated but not yet entirely resolved (Lee et al. 2010, Lerch et al. 2006).”
The Development and Application of Optogenetics (2011, methodology): “Recently, virally delivered optogenetic tools were used in rats to examine blood oxygen level–dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) (Lee et al. 2010).”
Activity flow over resting-state networks shapes cognitive task activations (2016, background): “…insights and the activity flow mapping procedure introduced here will facilitate future investigation into the functional relevance of resting-state FC, the factors that influence cognitive task activations and the balance of large-scale distributed versus localized processing in the human brain.”
Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement (2011, positive): “Most efforts to target genetically defined subpopulations of neurons in rats have relied on viral strategies (Lawlor et al., 2009; Lee et al., 2010), but since compact promoters are rare and viral vectors have limited packing capacity, published attempts often result in only partial specificity for…”