Hybrid neuroscience connects the dots for a big picture of the brain

To simultaneous manipulate and monitor living brain activity at both microscopic and macroscopic levels and identify the links to behavior is a significant goal of neuroscience. Thanks to a hybrid combination of optogenetics and functional magnetic resonance imaging (fMRI), this goal is being realized.

Two distinct methods, optogenetics and fMRI have working mechanisms that are completely different. Optogenetics combines genetic and optical methods to enable study the effect on brain function and behavior via manipulation or monitoring of specific cell populations, brain regions, or neural pathways. fMRI maps dynamic activities across the whole brain based on neural activity-induced hemodynamic changes. Combining these two technologies as "opto-fMRI" offers tremendous synergy in neuroscientific research.

As reported in Neurophotonics, scientists at Pennsylvania State University recently synthesized the history, technical advances, applications, and important considerations of optogenetics, fMRI, and their synergistic combination. The result is a useful overview and discussion of future directions for this hybrid method in neuroscience and neuroimaging.

Optogenetics and fMRI have each had tremendous impacts on science individually. Recent technological advances have allowed for the marriage of the two methods, providing valuable synergistic advantages to the fields of both neuroscience and neuroimaging. Previous attempts to use electrical stimulation during fMRI for electrophysiology resulted in interference between electrical and magnetic signals. The combination did not allow for a targeted manipulation of specific cell types or projections. Optogenetic manipulations and optical recording of neural activity are insensitive to MRI-related interference, and thus are well suited to be conducted alongside fMRI.

Opto-fMRI allows for the expansion of knowledge of a brain region and its whole-brain network from strictly anatomical to more of a functional understanding in awake and behaving rodents. Even in anesthetized rodents, opto-fMRI can be utilized to examine the network-level mechanisms that underlie the role of specific brain regions in certain brain/behavioral states. Targeted manipulation of brain region or cell-type, as well as targeted calcium activity measurement, can be linked with global brain signaling and behavior. Since its first emergence in 2010, opto-fMRI has proven useful in a wide variety of studies to advance neuroscience.

For instance, in neurovascular studies that examine the role of neural activity in the hemodynamic response, the addition of optogenetic manipulation to fMRI allows for the whole-brain visualization of the causal role of activating or inhibiting a specific cell type, defined by genetics, cell body location, or axonal projection target. As a crucial brain area for memory formation and retrieval, the hippocampus and its neuronal connectivity is an important target for the implementation of opto-fMRI.

Opto-fMRI can also be used as a tool for investigating the neural mechanisms behind less understood therapeutic applications, such as transcranial magnetic stimulation and deep brain stimulation (DBS). DBS is currently being used to treat disorders such as Parkinson's disease, epilepsy, chronic pain, major depression, and obsessive-compulsive disorder. However, the mechanism of action and effects on global brain functioning are not yet fully understood.

Read the open access article by Lauren N. Beloate and Nanyin Zhang, "Connecting the dots between cell populations, whole-brain activity, and behavior," Neurophotonics 9(3), 032208 (2022) doi 10.1117/1.NPh.9.3.032208.