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


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News Citations

  1. Where in the World Are the iPS Cells?
  2. Honolulu: Biomarker Profiles That Spell Trouble for ‘Normals’?
  3. Opto- and Pharmacogenetics: New Methods Shed Light on Brain Processes

External Citations

  1. Nature Neuroscience

Further Reading


  1. . Disease-specific iPS cell models in neuroscience. Curr Mol Med. 2013 Jun;13(5):832-41. PubMed.
  2. . Superresolution Imaging of Amyloid Fibrils with Binding-Activated Probes. ACS Chem Neurosci. 2013 Apr 22; PubMed.
  3. . Molecular tools and approaches for optogenetics. Biol Psychiatry. 2012 Jun 15;71(12):1033-8. PubMed.
  4. . Investigation of the effective connectivity of resting state networks in Alzheimer's disease: a functional MRI study combining independent components analysis and multivariate Granger causality analysis. NMR Biomed. 2012 Apr 16; PubMed.
  5. . Effect of transcranial brain stimulation for the treatment of Alzheimer disease: a review. Int J Alzheimers Dis. 2012;2012:687909. PubMed.
  6. . Preserved conceptual priming in Alzheimer's disease. Cortex. 2006 Oct;42(7):995-1004. PubMed.

Primary Papers

  1. . Opportunities and challenges of pluripotent stem cell neurodegenerative disease models. Nat Neurosci. 2013 Jul;16(7):780-9. Epub 2013 Jun 25 PubMed.
  2. . Opportunities and limitations of intrinsic functional connectivity MRI. Nat Neurosci. 2013 Jul;16(7):832-7. Epub 2013 Jun 25 PubMed.
  3. . Noninvasive brain stimulation: from physiology to network dynamics and back. Nat Neurosci. 2013 Jul;16(7):838-44. Epub 2013 Jun 25 PubMed.
  4. . Targeting neurons and photons for optogenetics. Nat Neurosci. 2013 Jul;16(7):805-15. Epub 2013 Jun 25 PubMed.
  5. . Optogenetic pharmacology for control of native neuronal signaling proteins. Nat Neurosci. 2013 Jul;16(7):816-23. Epub 2013 Jun 25 PubMed.
  6. . Probing perceptual decisions in rodents. Nat Neurosci. 2013 Jul;16(7):824-31. Epub 2013 Jun 25 PubMed.
  7. . Seeing the forest tree by tree: super-resolution light microscopy meets the neurosciences. Nat Neurosci. 2013 Jul;16(7):790-7. Epub 2013 Jun 25 PubMed.
  8. . Immunogold cytochemistry in neuroscience. Nat Neurosci. 2013 Jul;16(7):798-804. Epub 2013 Jun 25 PubMed.