26 Jun 2013

For the latest neuroscience techniques, their advantages and challenges, check out the June 25 online issue of Nature Neuroscience. In a series of eight reviews, titled "Focus on Neurotechniques," researchers describe how approaches such as optogenetics and stem cells are revolutionizing neuroscience, and explain the tricky issues scientists must overcome to reap the full benefits of the modern technologies.

In the stem cell review, Jackson Sandoe and Kevin Eggan of Harvard University point out that efforts to develop cell replacement therapy from stem cells led, somewhat unexpectedly, to the realization that those same cells could provide "neurodegeneration-in-a-dish" model systems. "These neurons enable the examination of processes not easily observed in postmortem tissues, including important events that might occur before disease onset," the authors write. However, they note important caveats. Two different pluripotent lines for the same disease may not offer identical results. And researchers do not yet understand how the cell lines may change or mature. "These and other sources of variation … may result in misleading ‘red herring’ findings," the authors write. "There are challenges that must be surmounted." (See ARF related news story.)

Randy Buckner of Massachusetts General Hospital and colleagues describe functional connectivity magnetic resonance imaging (fcMRI). Related to functional MRI, fcMRI identifies neural networks by correlating regions that act in sync in the resting brain. One study used the method to differentiate people with Alzheimer’s from those with mild cognitive impairment and controls (see ARF related news story). "The appeal of the technique lies in its simplicity," the authors write. "A brief MRI dataset acquired in resting subjects is sufficient to explore diverse brain systems." However, they caution that technical artifacts can cloud interpretation. For example, differences in the mental state of the people in the scanner can interfere, as do head movements.

Another review, by Botond Roska of the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland, and Adam Packer and Michael Häusser of University College London, U.K., addresses optogenetics. This is the use of light to turn neurons on and off via genetically encoded, light-sensitive ion channels. The technique has been used widely in neuroscience, including in experiments on Alzheimer’s and Parkinson’s (see ARF related news story). However, the authors note challenges in targeting the optogenetic signal as finely as one would like. For example, it is difficult to express light-sensitive proteins in specific neurons of non-human primates; here, virus-mediated gene transfer could offer a potential solution. Richard Kramer of the University of California, Berkeley, and colleagues present an alternative solution. They note that optogenetic pharmacology makes use of light-sensitive molecules that require no genetic programming, such as caged neurotransmitters. "Caged glutamate compounds give users the opportunity to rapidly and locally release a puff of agonist with spatial and temporal precision that rivals that of a real synaptic contact," they write.

The issue also includes reviews on noninvasive brain stimulation such as transcranial magnetic stimulation, perceptual decision-making studies in rodents, super-resolution light microscopy, and immunogold labeling for electron microscopy.—Amber Dance