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Brain Wiring For Fundamental Behaviors May Be Written In The Genome, No Learning Required

July 30, 2024 by Deborah Bloomfield

Somewhere in the savannah, a gazelle is born. A lick from mom and an uncertain wobble, and she is ready to run. Somewhere on a sandy beach, a little turtle hatches. It sits with its siblings under the sand, until, suddenly, they run as a group to the surface and straight into the sea. Have you ever wondered howanimals are capable of doing so much right from birth?

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For a brain to fully function, it needs to be wired correctly. A human brain has around 86 billion neurons, each connecting through thousands of synapses to other neurons. Some neurons are connected to their neighbors, others have to find their way over many centimeters (even up to a meter). How these connections are made has been debated for decades: How much of it is baked into the genome and how much of it arises from experience? Until now, the debate had landed somewhere in the middle, with a bit of both.

A recent study, however, is taking a stand. Not only is experience (of the senses, of motor programs, etc.) not necessary, but as a whole, neural activity – the electrical signals in neurons that allow them to communicate – isn’t necessary either. The brain is wired and ready to go based on genetics alone. The study took a rather radical approach: To find out if neuronal activity was necessary for development, they got rid of all of it.

“How much developmental activity is necessary for circuit assembly was just […] not known. […] The inspiration was to do it in a larval zebrafish, because that’s currently the only vertebrate […] where you can block all activity throughout development reversibly” senior author Dr. Florian Engert, Professor of Molecular and Cellular Biology at Harvard University, told IFLScience. “It wasn’t an experiment where we had an expectation for the outcome. We [were] just open for anything here.”

Removing neural activity or experience had previously been shown to affect normal development, but the perturbations had been localized. This created imbalances in the brain leading to compensation from unaffected regions. The brain is perturbation sensitive and is always targeting balance, according to Dr Engert, explaining the effects seen in these experiments.

Silencing the whole brain for several days is not an easy task. The researchers used a drug  called tricaine that blocks the electrical activity of neurons. They had to make sure the fish didn’t sensitize to the drugs. They also found out that the drug was breaking down into toxic compounds in light, so they had to rear the fish in darkness. But, after several rounds of testing, they succeeded in their experiment. In adult fish it can be lethal, but the larval fish lived! They were small enough that they could breathe through their skin, and eat from their yolk sac. Turns out, you don’t need a brain to grow up. 

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To test if the silencing had an effect, they tested the fish for their optomotor response (OMR), where zebrafish turn to align themselves to the speed and direction of whole-field visual motion. This is thought to allow them to stay stationary in a moving stream. OMR and the neural circuitry underlying it are very well characterized in zebrafish, making it ideal for this study. “The [OMR] requires temporal integration, evidence accumulation and gain control, […] which link to learning, memory and decision making” says Dr Engert “So [it] actually captures a lot of the other aspects of higher order, cognitive-like behaviors.” 

After three days living in tricaine-infused water, the larval zebrafish woke up from their drug-induced quiescence with intact neural circuitry ready to perform OMR. The lack of neural activity didn’t have an effect, the fish brain had everything it needed in the genome. “The connection and the initial assembly of a connectome is happening in three stages. The first is differentiation, and soma position. You put all the individual units in the right place and give them the right signature. The second one is axon growth, axon guidance along morphogenetic gradients, all under genetic control. And the final stage is cell-cell recognition, is finding your synaptic partners.”

“In basically all animals most of the critical, if not all behaviors, are already there when the animal engages the world.” says Dr Engert “Knowledge, competency, and skill, expertise, cognitive power is all baked into the genome. In no animal, anything critical needs to be learned.” So is everything hard coded? It’s not fully deterministic, according to Dr Engert. In the vertebrate brain there is also a “stochastic element of wiring”.

If we’re born ready to go, what happens after birth? At first, “You need to constantly recalibrate because things are still changing” because your body is still growing. “If you want to observe the calibration in action, you should watch a movie of a newborn horse when it’s born. And for the first ten minutes they stumble around uncoordinated, but you can really see it in real time. You can see […] how the system calibrates itself.” 

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Maybe a young horse is able to run soon after birth, but have you seen a human baby? According to Dr Engert, humans, like monkeys and other animals, are essentially born prematurely. That doesn’t mean experience after birth is necessary for early development. On top of that, as humans we depend on a lot of acquired knowledge because language is so central to our social and cognitive behaviors. A fully functional human requires more experience to shape the brain than what is present at birth.

The problem of how much our brains are wired without experience is interesting for neural networks as well. “Research in artificial intelligence and computational neuroscience have highlighted how weakly structured models can learn to perform complex tasks” say the authors. Unlike most neural networks, much of the brain’s functional wiring is established without learning.

This study is published in the journal Nature communications

Deborah Bloomfield
Deborah Bloomfield

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