TED TALK: Understanding the brain by controlling neurons – Gero Miesenboeck reengineers a brain

Gero Miesenboeck reengineers a brain

Optical mind control.
In this case the brain is controlled to explain how it works.

The general neuroscientist ascribes to this statement:
” If we could record the activity of all neurons, we could understand the brain.”

But if we could measure the activity of all neurons we would still have to make sense of the recorded activity patterns. But it is quite difficult to understand these patterns.

1:55 shows the pattern of only ten thousand neurons firing. roughly 1% of the brain of a cockroach. Each black dot represents one neuron. Our brain are about 100 million times more complicated.
Harbored in a pattern like this is You. Your emotions, perceptions, thoughts, plans for your future. But we do not understand this since we do not know how to read this pattern and we do not understand the code used by the brain.
To make progress we need to break the code. But how?

An experienced code breaker will tell you in order to break a code it is essential to be able to play with the pattern and rearrange it at will.

So to decode the information from a neuronal pattern, we need to be able to rearrange it .

Ie. Instead of recording the activity of all neurons, we need to control it.
The more targeted our interventions the better. The ability to control neurons will not unravel all mysteries, but will certainly allow us to learn a lot.

So to rephrase the above quote :
” If we could CONTROL the activity of SOME neurons, we could LEAEN MJUCH ABOUT the brain.”

Intervention is a powerful tool where there is a rich history of tinkering with the nervous system. Galvani showed 200 years ago that frogs legs twitched when the lumbar nerve is connected to a source of electric current. This was the first experiment to reveal that most fundamental nugget of neural code, and it is that information in the nervous system is written in the form of electrical impulses. This approach of probing the nervous system with electrodes remains state of the till today although it has some drawbacks.
Drawbacks: sticking wires to the brain is rather crude and there is a physical limit to the number of wires that can be inserted simultaneously.

So what if we take this logic and turn it upside down. Ie. Instead of inserting a wire into one spot of the brain, we could reengineer the brain itself so that some of neuronal elements become responsive to diffusely broadcast signal such as a flash of light. Such an approach will overcome many of the obstacles to discovery.
This method serves as
1. Non-invasive wireless form of communication
2. Just like a radio broadcast, you can communicate with many receivers at once, you don’t need to know where these receivers are and it doesn’t matter if these receivers move. These receivers can be fabricated out of the DNA code.
Ie. Each nerve cell with the right genetic makeup will spontaneously generate a receiver that will allow us to control its function. BIOLOGY REVEALED THROUGH BIOLOGY.

Miraculous receivers.
The outer membrane of neurons is coated with microscopic pores which conduct electrical current and are responsible for all the communication in the nervous system. these pores, however, are special (similar to retina) in that they are sensitive to light. When a flash of light hits the receptor, electrical current is switched on and the neuron fires an electrical impulse.

As a result of these light activated pores encoded in DNA, we can achieve incredible precision. All cells contain the same set of genes where some genes are turned on and off in different cells. We can exploit this to make sure that a desired set of neurons contains these light activated pores.

This approach works well such that we can write purely artificial messages directly to the brain.
07:07 Each electrical impulse shown on the grid represents a brief pulse of light.

Remote control of behavior
This approach also works in moving behaving animals. In the experiment conducted by the speakers student, 2 out of a possible 200,000 cells in the fruit flies brain were engineered to express the light activated pore. These targeted cells trigger the cape reflex that makes the fly jump.
Control experiment: the heads of the fruit flies were cut. (They could live for a day like this, standing around and grooming excessively). The flight mode – which is the equivalent of the spinal cord of these flies- was able to be turned on, making these headless bodies take off and fly away.

Enter the field of OPTOGENETICS

Many labs use this approach. We can now interfere with the psychology of fruit flies in rather profound ways.

What to do next
Life is a string of choices creating a constant pressure of what to do next. We cope with this pressure by having brains. Within our brain are decision making centers that are labeled the ‘actor’. The actor implements a policy that takes into account the state of the environment and the context by which we operate.
Our actions change the environment and the context and these changes are then fed back into the decision loop.

To explain this from the perspective of neurobiology, a simple one dimensional world was constructed for the fruit flies.

Chambers containing one fly arranged as 2 vertical stacks. the left and right chambers are filled with two different odors. A security camera watches as flies move around. Whenever a fly reaches a midpoint it must make e decision of staying in the same odor or try a new one. This represents the actor’s policy.
The policy is not written in stone and changes as the fly leans with experience.
We can incorporate an element of adaptive intelligence into our model by assuming that the flies brain contains a different group cells that provides a running commentary on the actors choices: The critic. (This is the brain equivalent of your mother or the church).

The critic is a key ingredient into what makes us intelligent.
Next step was to identify the cells that in the fly’s brain that played the role of the critic. Using the optical remote to activate the cells of the citric, the fly could be artificially induced to change its policy. In other words, the fly learns from mistakes it tough it had made, but in reality they were not made and were induced artificially.

Searching for the critic within

Experiment. Fly’s with brain peppered with cells that were light inducible were bred. The flies were allowed to make choices. Whenever one odor was chosen, the light was turned on. If the critic was among the optically activated cells, the result of this intervention should be a change of policy where the fly learned to avoid the optically reinforced odor.

Optically activating about a hundred dopamine producing cells in different areas of two flys had dramatic effects. Right hemisphere dopamine cells in one, left hemisphere dopamine cells in the other.

One fly crossed the odor barrier while the other stayed within one odor. This means that the policy the actor of the second fly implements includes an instruction to avoid the other odor. The critic must have spoken in this fruit fly and the critic must be contained within dopamine producing cells on the left of the brain. This way the identity of the critic was broken down to twelve cells.

The twelve cells send output to brain structures to a mushroom body. According to the model, the critic send its output to the actor, so the anatomy suggests that the mushroom body has something to do with action choice.
This makes sense such that an electrical toy circuit able to detect smell was developed.

Toy circuit that simulated the behavior of the fly

Mushroom body neuron are symbolized by the vertical bank of blue LED’s.
the LED’s are wired to sensors that detect the presence of odorous molecules in the air.
Each odor activates a different combination of sensors which in turn activates a different odor detector in the mushroom body.
So the actor can tell which odor is present by looking at which LED lights up.
What the actor does with this information is stored in its policy which is stored in the strengths of the connection between the odor detectors and the motors the fly’s way of action. If the odor is weak, the motor will stay off and the fly’s will continue straight in its course. if the odor is strong the fly will initiate a turn.

Consider a situation where the fly continues in its course but gets zapped. In such a case we would expect the critic so speak up and to tell the actor to change its policy. This was created artificially by turning on the critic with a flash of light. That caused a strengthening of the connection between the currently active odor detector and the motor. I.e. next time the same odor is encountered the connection is strong enough for the fly to turn on its motor triggering an invasive maneuver.


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