The Nature of the Beast by David J. Anderson

Author:David J. Anderson [J., David Anderson]
Language: eng
Format: epub
Publisher: Basic Books
Published: 2022-03-15T00:00:00+00:00

WHILE WE WERE WRESTLING with these questions (around 2006–2007), revolutionary new techniques were being developed by neuroscientists Karl Deisseroth and his postdoc Ed Boyden at Stanford for artificially stimulating neurons using light. This technique was a variant of a suite of tools, including some initially pioneered by Oxford neuroscientist Gero Miesenbock, collectively called optogenetics. I’ve already mentioned this technique briefly in some of the previous chapters—we used it to activate fear neurons in mice and aggression neurons in flies—but it’s worth going into it in a bit more detail because it’s so central to the work described in this chapter.

The overall principle is based on the fact that neurons are electrically excitable cells—once you let a few positively charged ions flow into them from the salty solution that bathes them, they get activated and start firing, producing pulses of electricity that flow along their axons. It’s kind of like starting a fire: the neuron has all the firewood built into it, and all you have to do is provide the match. Normally neurons are sealed against ions (otherwise they’d be firing all the time), but there are proteins called ion channels that penetrate the surface membrane that surrounds the cell. These channels can open special tunnels in the membrane, through which salt ions (like sodium) can flow into the cell. Each ion channel needs some source of energy to open the tunnel and let ionic traffic through. In a certain class of channels, called opsins, that source of energy is light of a particular wavelength (see Chapter 4). Some opsins can be activated by blue light, others by red light, according to their molecular structure. So if you genetically engineer a light-activated ion channel into a neuron and shine light of the appropriate wavelength onto the cell, sodium ions will flow into the cell and the neuron is going to start firing (Figure 6-1A). Hence the term “optogenetics.”

While mammalian neurons have plenty of ion channels, the vast majority are not activated by light (which can’t easily penetrate the skull to reach cells deep in the brain). Opsins are unusual and mainly found in microorganisms. For example, the single-celled alga Chlamydomonas rheinhardii contains a blue-light-activated ion channel called channelrhodopsin-2 (ChR2) in its membrane. When ChR2 absorbs blue light, it lets sodium and potassium ions flow into the cell. That electrically activates the alga and helps the little beast swim toward the light source with the aid of a tiny appendage called a flagellum, which whips back and forth like the tail of a swimming sperm cell.

Thanks to the pioneering work of biochemist Peter Hegemann and molecular biologist Georg Nagel in Germany, it was shown that the ion channel in ChR2 could be directly opened by blue light in a foreign cell that normally does not contain the gene—for example, a frog egg. That’s because, conveniently, ChR2 is both a light sensor and an ion channel, all in one. And because the genetic code is essentially universal, when Deisseroth and Boyden implanted the ChR2 gene (i.

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