Controlling Worms with Light

A new optogenetics system can stimulate neurons in an entire population of moving worms simultaneously, exquisitely controlling when they dash forward, back up, or turn around.

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A new optogenetics system can stimulate neurons in an entire population of moving worms simultaneously, exquisitely controlling when they dash forward, back up, or turn around.

The "optogenetic illumination system" delivers light to specific regions on each worm's body, such as its head or tail, and can even be programmed to deliver pulses of light in response to a worm’s behavior.

The study, by Liu et al., appeared in PLOS Biology in January.

Fig 1. Closed-loop targeted optogenetic delivery system. (a) Schematic of system. (b) Photograph of instrument. (c) Animals expressing Chrimson in touch receptor neurons (AML470) as they crawl on agar. Tracked paths are shown in yellow. Inset shows details of an animal receiving optogenetic stimulation targeted to its head and tail (0.5-mm diameter stimuli). © 2022 Liu et al.

At a basic level, optogenetics works like this: Neurons are engineered to express channelrhodopsins, or opsins, that dot the cell’s extremities. These proteins morph their shape when struck by light, forming pores that usher sodium ions into the cell to trigger an action potential. In fruit flies and worms, optogenetics has already been used to study the neural circuits underlying chemotaxis, olfaction, learning, memory and movements.

What happened?

Worms were engineered to express an optogenetic protein, called "Chrimson," in just six of their neurons. About 40 worms were placed in a small petri dish. A projector, overhead, split red light (630 nm) and cast it, like Broadway spotlights, down on the worms. A camera, placed beneath the petri dish, tracked each worm's movement in real-time and fed that data to the computer. The projector moved around the light, stimulating neurons in each worm's head or butt as desired.

What's new?

A few things. The computer vision software, which tracks both the 'pose' and behavior of each animal, was custom-made. The hardware setup is fast and flexible. It can deliver pulses of light 25-fold faster than a prior method and, in the future, it could deliver red and blue light simultaneously, the researchers say, "to independently activate 2 different opsins such as the excitatory red opsin Chrimson and the inhibitory blue opsin gtACR2."

Why worms?

C. elegans is a useful model to study the link between neurons and motor coordination because they have exactly 959 somatic cells, 302 of which make up the ganglia, or primitive brains, within their head and tail. The lineage of each cell has been mapped, which means we know where it came from and, in most cases, what it does.

These worms are also transparent. This makes them ideal for optogenetics experiments, because the light can penetrate their outer layer and stimulate neurons non-invasively.

What are the findings?

More than 43,000 optogenetic stimuli were delivered to the worms and recorded. From that data, the researchers found:
- By activating neurons in both the head and tail, at the same time, the worms were more likely to 'sprint' forward.
- The probability of a worm reversal was mainly driven by activating neurons in the head.
- Excitatory signals delivered as a worm turns appear to get partially blocked. Activating neurons in the head, for example, was less likely to make a worm reverse if the animal was already turning.

The optogenetics illumination system can track at least 40 worms at once. If a worm moved 200 microns per second, the system's spatial resolution was about 40 microns.

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More soon,

— Niko