神经损伤与修复
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Figure 1 ｜ Optogenetics and neuroregeneration.
Optogenetics is a powerful technology that employs light and genetics to manipulate physiology and behavior with unprecedented precision. The high acuity of light stimulation permits fine control both in space (e.g., to target just one tissue in an animal) and in time (e.g., to interfere with a specific disease stage), whilst genetic targeting restricts manipulation to a functionally-relevant cell population (Figure 1A).
Optogenetics refers to the genetic targeting of photoreceptor proteins, e.g. using cell-type-specific promoters or cell-type-specific gene recombination, to achieve light-induced responses only in a subset of functionallyHarald Janovjak* , Sonja Kleinlogel relevant cells. In 2002, a seminal study demonstrated that expression of an exogenous Drosophila opsin can render cultured hippocampal neurons lightsensitive (Zemelman et al., 2002). Specifically, light stimulation resulted in action potential firing only in the transfected neurons of the otherwise homogenous preparation. One limitation of the employed system was that three genes, the opsin, a G-protein α-subunit, and an arrestin, were required for functional light responses, somewhat complicating potential in vivo applications. The discovery of channelrhodopsins (ChRs), in particular channelrhodopsin-2 from the green alga Chlamydomonas rheinhardtii (Nagel et al., 2003), was a key step towards the broad uptake of optogenetics. Chlamydomonas rheinhardtii naturally exhibits rapid photocurrents and ChRs encode relatively small (~300 amino acids for truncated variants) “stand alone” light-activated ion channels. Since this discovery, ChRs have become instrumental in optogenetics and answered long-standing questions in neuroscience and beyond. The ChR breakthrough was followed by several major waves of development. First, new microbial opsins were discovered and existing opsins were reengineered towards neuronal silencing, increased light sensitivity, and multi-color experiments. Second, further microbial, plant, and even metazoan photoreceptor classes were employed for control of a wider range of cellular processes, including enzyme activity, intracellular signaling, and gene regulation (Figure 1B).
The ability to spatio-temporally control neurons has been harnessed for the restoration of lost neurosensory functions, including vision and hearing (Figure 1C) (Kleinlogel et al., 2020).