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Explainer: What is Optogenetics?

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Helping scientists better understand neural processing.

new mri techniques, what is brain mapping and how does it work, optogenetics mit

“….The advent of MRI mapping techniques using intrinsic blood-tissue contrast promises development of a functional human neuroanatomy of unprecedented spatial-temporal resolution…may allow for investigation of information processing at several levels of organization-ranging from neural systems to neural networks….”. Since such modest beginnings to mapping human brain activity using functional MRI, it has grown to being considered a gold standard imaging modality with an average of 1000 papers published per year over the last decade.

Dream experiments
Recently, another technique that’s caught the eye of many a neuroscience researcher is Optogenetics; chosen in 2010 as the Method of the Year by Nature Methods journal. The basis of this technology is that function of opsin tagged neurons can be modified by shining appropriate wavelengths of light on them. A recent review by Packer et al. in the current issue of Nature Neuroscience is an excellent compilation of the current state of this technology. It also outlines some of the advances that need to be made – development of better molecular genetics tools and also the optics used to stimulate those opsins – to be able to completely tap the potential of this method in performing some ‘dream experiments’.

Specifically, Packer et al. propose easier optimization and need for better safety measures to grow the virus vectors; make them less toxic to enable longitudinal imaging; and ensure that targeting not only be made simpler but also be based on activation rather than genetics. In terms of the optics, the authors stress on the need for improved focused targeting such that only the relevant cells are activated, ensure light scattering is reduced, enable efficient readouts to provide proper feedback to the experimenter, and improve light delivery methods for easy integration with other imaging modalities.

The authors suggest that such ‘targeted optogenetics’ ideas can eventually help answer fundamental questions in neuroscience. For example, help define cell types based on combining anatomical, genetic, and physiological definitions, to determine sparseness, i.e., does one nerve cell have the ability to influence the function of an entire circuit; thereby modulating behavior, and also perform experiments that can crack the neural code; wherein a particular behavior can be determined by the spatiotemporal activation patterns of excitation and inhibition within a set of genetically modified cells.

Boyden et al.’s first paper on optogenetics in 2005 concluded “….Thus, the technology described here may fulfill the long-sought goal of a method for noninvasive, genetically targeted, temporally precise control of neuronal activity, with potential applications ranging from neuroscience to biomedical engineering.” Optogenetics has already advanced leaps and bounds, aided by its ability to integrate with many other modalities including fMRI, in helping scientists better understand neural processing.

But, to really see how far it can go, we may have to wait much longer. Along the way, could this be ‘the technology’ that helps accomplish the President’s BRAIN initiative mission? In the meantime, does fMRI need its own Method of the Decade recognition?

References:

  1. Boyden ES, Zhang F, Bamberg E, Nagel G, & Deisseroth K (2005). Millisecond-timescale, genetically targeted optical control of neural activity. Nature neuroscience, 8 (9), 1263-8 PMID: 16116447
  2. Kwong KK, Belliveau JW, Chesler DA, Goldberg IE, Weisskoff RM, Poncelet BP, Kennedy DN, Hoppel BE, Cohen MS, & Turner R (1992). Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proceedings of the National Academy of Sciences of the United States of America, 89 (12), 5675-9 PMID: 1608978
  3. Packer AM, Roska B, & Häusser M (2013). Targeting neurons and photons for optogenetics. Nature neuroscience, 16 (7), 805-15 PMID: 23799473

new mri techniques, what is brain mapping and how does it work, optogenetics mit

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