Combining functional magnetic resonance imaging (fMRI) of rat brains with a technique that uses light to detect neuronal activity can help researchers hone in on the source of the activity, according to a study published 6 May in Nature Methods1.
To identify the brain regions involved in a particular task, researchers often rely on fMRI, a non-invasive imaging method that detects changes in blood flow and oxygen levels in the brain. But this is an indirect measure of neuronal activity, and cannot determine whether neurons in the region are sending or receiving a signal. It also cannot discriminate between the activity of neurons and other brain cells, such as glia, which are support cells in the brain.
Researchers have used animal studies to address some of these issues. In one study, they scanned monkey brains while using an electrical probe to record neuronal activity. However, the metal probe can interfere with the magnetic signals detected during fMRI, making it difficult to interpret the results2.
In the new study, the researchers combined fMRI with a technique that records the activity of neurons using light rather than electrical activity. This allowed them to use a small optical probe inserted into a rat’s skull, which they found does not interfere with fMRI signals.
The researchers gave rats sitting in an fMRI scanner a slight shock in their front paws, and then recorded the response in the somatosensory cortex, a brain region that responds to touch. They also detected neuronal activity by injecting rat brains with an indicator dye that fluoresces in response to calcium, which is released when neurons fire.
Neuronal activity is so closely tied to the fMRI signal that in some cases one can predict the other, the study found. However, by using a dye that discriminates between neurons and glia, the researchers found that in some cases glial activity, rather than neuronal activity, contributes to the fMRI response.
The results suggest that interpreting these fMRI signals is not as simple as previously thought, the researchers say.
The researchers also plan to use techniques such as to detect signaling from certain subpopulations of neurons. For example, researchers could express a different indicator in neurons that inhibit signals compared with those that activate signals and parse out the relative contribution of each to an fMRI response.
1: Schulz K. et al. Nat. MethodsEpub ahead of print (2012) PubMed
2: Oeltermann A. et al. Magn. Reson. Imaging 25, 760-774 (2007) PubMed