Whole-brain imaging of mice during behavior

"Functional ultrasound imaging yields images in much higher resolution and is simpler, less expensive and easier to use than functional magnetic resonance imaging (fMRI)," explains Botond Roska. "Most importantly, the technology allows us to study the consequences of ophthalmologic diseases, monitor the effect of treatment and the progress of rehabilitation in the whole brain in mice."

Large numbers of brain regions are active during behaviors. Brain-wide activity maps can lead to a system-level understanding of how brain activity relates to specific behavior. The international team of scientists from the Institute of Molecular and Clinical Ophthalmology Basel, the FMI, and the Neuro-Electronics Research Flanders, has developed high-resolution functional ultrasound imaging to record activity in the whole brain of mice during behavior. This has not been possible so far with animal models, because current whole-brain functional imaging technologies, such as fMRI, are limited in resolution and difficult to apply to awake and behaving mice.

The team was particularly interested in the brain regions involved in the optokinetic reflex. The optokinetic reflex stabilizes images drifting on the retina both horizontally and vertically by moving the eye in the direction of image drift. For example: as we look out of a train window our eyes reflexively move to follow the passing landscape. This reflex is inborn and well conserved across species, from mice to humans.

In their study, the researchers found that out of the 181 brain regions consistently identified in all animals, activity in 87 regions across the whole brain were modulated during the optokinetic reflex.

To study the function of these brain regions, the team compared brain activity in healthy mice with mice who lack the optokinetic reflex -- either because of a genetic disease that makes the retina incapable of generating the reflex, or because eye motion was mechanically blocked. The majority of brain regions active upon eye movement in normal mice become inactive in mice with the genetic disease, showing that they are involved in generating the reflex. Among those regions, some regions in the thalamus are particularly interesting: they still respond in normal mice whose eye movements are blocked, but not in mice with the genetic disease, showing that they are independent of the motor output of the reflex.

First author Emilie Macé, a postdoctoral fellow in Botond Roska's group, who developed the concept of functional ultrasound imaging while working in Paris, commented: "We were surprised how precisely we could map activity across the brain and how many brain regions became active during this reflex. Our brain-wide approach revealed new regions that can now be studied more precisely in attempts to understand the logic of sensorimotor transformations at the level of microcircuits." Botond Roska also highlights the value of the technology for future application in different medical fields: "The simplicity, low cost, and ease of use of whole-brain functional ultrasound imaging, together with the ability to precisely identify brain regions, provides a system for obtaining an unbiased view of brain activity in other types of behavior as well as in animal models of neurologic or psychiatric diseases."