How does opsin work

Optogenetics relies on light-responsive proteins called opsins to selectively turn neuronal activity on or off with a flash of light. Optogenetics controls whether or not this signal is sent. To understand how optogenetics does this, it is important to understand how neurons function normally Figure 1. Whether or not a neuron fires depends on the flow of positively- or negatively-charged ions across the membrane.

In general, when more positively charged ions enter, the neuron will fire. When more negatively charged ions enter, the neuron does not fire. Opsins play their role by controlling which ions enter the neuron. When activated by blue light, channelrhodopsin lets positive ions enter the neuron.

Halorhodopsin is also not found in humans but rather in single-celled organisms called Archaea. How does this activation work? This technology has been useful for researchers studying neuronal connections and their functions in the brains of rodents and other research models.

However, recent advances are taking optogenetics to the clinical level. The genetic material required for a cell to make an opsin is packaged into a gutted virus that can deliver the opsin, but does not cause disease. Researchers then inject this virus into a target area and cells that take up the virus can then make opsins. When they activated the opsin noninvasively with light through the bottom of the cage, the mice experienced pain. They absorb yellow-green, green, and blue-violet, and the signals are then combined by the brain to give a view in color.

Cone cells are less sensitive to light than rod cells. The transmission of visual information to the brain is only one type of signal relayed by opsins. Another type is relayed by melanopsin , an opsin more similar to invertebrate opsins. It responds to light and transmits a non-visual signal that translates the need for sleep to a 24 hour light-and-dark cycle, known as the circadian rhythm. Blind people with functioning retinas can still adhere to this cycle.

Because each opsin responds to a specific type of light, we could use different light to control different types of neurons. In fact, some opsins act to turn neurons off when the right type of light is present. In our example of mapping cars in the city, we could use multiple signals to control the movement of the cars. We could have one set of cars go out on the road when we give one signal say, blue light and another set of cars go out on the road when we give a different signal say, a red light.

Using this setup, we could start experimenting with these two sets of cars: what happens if the red light cars go first? What happens if the blue light cars go first? What happens if they go at the same time? This would help us to understand how these different sets of cars interact with each other. So how does a scientist choose which technique or which opsin to use? The answer will depend on the question the scientist wants to explore. The next section will highlight some of the questions that have been investigated using optogenetics.

Brain scientists began using optogenetics in [ 3 ]. Since then, optogenetic methods have been used to study the brain from many different points of view—from the communication of a cluster of individual neurons, to the interactions between large brain regions reviewed in Ref. Many other studies have used optogenetic methods to investigate different topics and questions. Some recent questions are: where is fear in the brain?

How is risk and reward calculated? How are memories stored? We used optogenetics in mice to investigate how the brain changes after a stroke [ 7 ]. A stroke happens when the blood supply to an area of the brain is disrupted or reduced. This is dangerous because the blood supply carries oxygen and other important nutrients that the brain needs to survive. If any area of the brain goes for too long without oxygen, the neurons in that area will eventually die.

This causes problems for that particular area of the brain and for any other brain areas that are connected to it. In our study, we wanted to investigate how a small stroke to one area of the brain affected many other areas of the brain. To begin, we used ChR2 to help us draw a functional map of the mouse brain. We compared the maps between animals with a stroke and without a stroke. We found that the maps changed over time.

At 1 week after stroke, the overall brain activity was very low. Surprisingly, activity was low even at an area far away from the stroke. By 8 weeks after stroke, the overall brain activity was higher, but not back to normal. From these data, we concluded that even a small stroke can have a big effect on how the brain works as a whole. Understanding what happens to the brain after a stroke could help scientists create better treatments for stroke patients.

This is just one example of how useful optogenetics can be for investigating questions about the brain. It is likely that brain scientists will continue to use optogenetics for many years to come.

There are billions of neurons in the brain, and the signals sent between these cells are the basis for all of our thoughts and behaviors. Neurons are sometimes called nerve cells. This causes changes in the electrical activity of the tissue. Genetic engineering is sometimes called genetic modification. When light hits the rods and cones, the photopigments catch the light and activate a cascade of second messenger reactions, eventually causing hyperpolarization of the membrane.

This hyperpolarization in turn activates secondary neurons in the retina, which eventually carry the receptor signal to the brain, where it is processed and used to generate a visual percept.

Light sensing across single-celled and multicellelar animals is mediated by two large families of proteins: the opsins. Opsin genes are divided into two distinct superfamilies: microbial opsins type I and animal opsins type II.

The rohodpsin and cone pigments found in humans belong to type II. Among other differences, type I opsins are bound to ion channels, while type II is not.

Type II opsins therefore need a battery of intracellular second messenger molecules to operate. In contrast, the type I opsins, being channel proteins, directly cause intracellular changes by changing the membrane potential upon activation due to ion flow.

Type I opsins, being channel proteins are referred to as channelrhodopsins. In retinal degenerative diseases such as retinitis pigmentosa RP the photoreceptors degenerate and patients eventually loose their vision.

The secondary neurons in the retina, however, partly survive. As explained above, these secondary neurons are responsible for processing the photoreceptor signal and sending it to the optic nerve. Hence, although RP patients miss the photoreceptors, the rest of the visual pathway is ready to rock! Hence, somehow these neurons should be activated. There are a battery of approaches to do just this. Retinal implants activate the neurons directly by electrical activation see further reading 3.

Optogenetics Fenno et al. The neurons are made photosensitive by making them express channelrhodospins. This is done by injecting a viral vector into the eye such that the virus infects the retinal cells. Instead of a viable virus, however, it is tinkered aound with and the only thing the virus does is incorporate the channelrhodopsin into the genome of the neurons, which start to express it.

This depolarizes the neuron and can induce action potential firing see further reading 1. Action potentials is the neuron way of transmitting signals to the brain. Hence, by activating the secondary neurons through channelrhodopsin transformation, they start sending light-induced neural activity to the brain.

The brain will handle this input as if evoked by photoreceptors and hence will interpret it as light-evoked visual stimuli. With regard to cancer: It has been shown that expression of channelrhodopsin and illumination of whole-mice resulted in diminished subcutaneous cancer cell counts yang et al. With regard to your first added question: dependent on the exact peptide regulatory sequences added to the protein, or by using viral vectors specifically targeting axons, expression of channelrhodopsins can occur wherever one likes.

Your second added question: Cation channels activate neurons, anion channels inhibit them. This means you can play around with different variants to control neurons at will.

References Fenno et al. Annu Rev Neurosci ;— Yang et al.