Optogenetics is a technique to manipulate genetically-defined neural activity with light, and it has two main advantages:

  1. Millisecond Temporal Precision 
  2. Genetically-Defined Spatial Precision

Temporal precision enables researchers to turn neurons on or off with millisecond timing. This fast timing can closely mimic the firing rates of neurons in the brain. 

Spatial precision enables researchers to manipulate the activity of genetically-defined neuron populations (e.g., inhibitory neurons). This provides a causal link between the manipulation of the genetically-defined population and the variable being measured.

In optogenetic experiments, only neurons expressing the optogenetic probe are controlled, leading to activation or inhibition of those neurons.

However, standard optogenetic light sources can only illuminate the entire field of view and, as a result, they stimulate all neurons expressing the optogenetic probe. Such a system may be adequate for some experiments in which all optogenetic-expressing neurons can be stimulated at the same time, but more advanced experiments may require the specificity to selectively stimulate individual neurons within the field of view.

The ability to illuminate select neurons within a population of optogenetic-expressing neurons is called cellular-resolution optogenetics (Shemesh et al. 2017). This method requires more sophisticated spatial specificity to selectively stimulate individual neurons within an optogenetic-expressing population.

Comparison between widefield and cellular-resolution optogenetic stimulation.

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Optogenetic Stimulation: The Ultimate Guide

The ability to illuminate certain individual neurons is not a limitation of optogenetics, but a limitation of the standard optogenetic light sources used in most optogenetic systems. Standard light sources can only illuminate all cells within the field of view, and they cannot control where they illuminate to target individual neurons.

The development of spatially targeted light technologies has enabled researchers to control where light illuminates the sample, such as an individual cell, making cellular-resolution optogenetics possible (Ronzitti et al. 2017). For example, a digital micromirror device (DMD), such as Mightex’s Polygon, allows researchers to illuminate multiple individual neurons or regions simultaneously to perform cellular-resolution optogenetics.

Cellular-resolution optogenetics has multiple applications in the field of neuroscience. For example, scientists can study neural circuits and decode neural patterns at the level of individual neurons (Anastasiades et al. 2020; Tran et al. 2019). These types of studies have been carried out both in vitro and in vivo using different technologies (Shemesh et al. 2017; Anastasiades et al. 2020; Tran et al. 2019; Chen et al. 2019). The experimental applications for cellular-resolution optogenetics are endless.

Next Post

What Systems are Available for Cellular-Resolution Optogenetics? (Part 1)


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Free eBook Download
Optogenetic Stimulation: The Ultimate Guide