Study: Vision in the brain – hardwired for action

(Image Credit: AdobeStock/kazakovmaksim)

Researchers at the Max Planck Institute for Biological Intelligence, in their study¹ of a genetic mutation in zebrafish that eliminates all connections between retina and brain throughout development, have found that animals possess specialized networks of neurons in the brain that receive signals about the outside world from the retina and respond by initiating appropriate behavior.

According to a news release from the institute, researchers found that in these ‘deep-blind’ fish the brain circuits are fully functional, as direct brain stimulation with optogenetics can drive normal visual behavior. The researchers pointed out this shows that the assembly of the brain in zebrafish requires little, if any, visual experience.

The research noted zebrafish, much like humans, depend on their vision. As a result, large parts of the brain are dedicated to processing visual information, and vision is crucial for the animal to find food and navigate its environment. Much like human infants, young zebrafish learn from experience. They like familiar food and memorize where they found it. A portion of the process is the development of new connections between brain cells and the fine turning of old ones.

“When we study brain development, we broadly distinguish between innate and experience-dependent processes,” Herwig Baier, director at the Max Planck Institute for Biological Intelligence said in the news release. “The assembly of neuronal circuits, for example in visual brain areas, is classically considered an experience-dependent process: the neuronal networks are thought to be shaped by visual inputs and neuronal activity.”

But what happens if the visual information is never there in the first place?

In an effort to come up with an answer, the researchers examined just how animals like fish or mice develop when they grow up in the dark. In this case, the brain is deprived of visual experience – but the eyes still send many signals to the brain.

Neurons in the zebrafish brain that normally receive input from the retina develop just fine without that input. Surprisingly, the neurons are able to drive behavior even if they have never been in touch with the visual world. Some of these neurons and their axonal connections to motor centers are depicted here. (Image courtesy of Max Planck Institute for Biological Intelligence/Herwig Baier)

The retina normally converts patterns of photons that hit the back of the eye to patterns of electrical impulses, which are then transmitted to the brain by retinal ganglion cells, which store information that animals have about the visual surroundings. But this is not the only way in which the eye can talk to the brain.

Neurons generate their own activity

Retinal ganglion cells generate their own neuronal activity during development. At times, electrical activity waves can sweep across the surface of the retina, travel to the central brain areas and refine the synaptic connections. In addition, the axons of retinal ganglion cells secrete molecular factors that are received by cells in the central brain and induce developmental changes. The signals may form the circuitry of the brain. Previous studies examined just at the effects of these factors in isolation and analyzed, for instance, how blindness affects brain development.

“To really understand how brain development depends on stimulation from the eyes, one needs to look at what happens when retinal ganglion cells are taken out of the equation,” Shachar Sherman, lead author of the study, said in the news release.

A graduate student in Baier’s department, Sherman and his colleagues examined a zebrafish mutant known as lakritz, which have a genetic defect that prevents retinal ganglion cells from forming. The defects are restricted to the eye. If not for their dark color one wouldn’t be able to tell the difference between mutants and their wildtype siblings.

“The lakritz mutant is not just blind; it is deep-blind. Its brain is entirely disconnected from the visual world and any retina-derived signals,” Baier said in the institute’s news release. “This unique situation opened up the possibility to study the influence of retinal ganglion cells on brain development and behavior in a systematic and comprehensive fashion.”

The researchers raised young lakritz zebrafish and compared their brain development to zebrafish without the genetic defect. The department mapped out a virtual cell atlas of the brain of the zebrafish.

“To our surprise, we didn’t see much of a difference,” Sherman said in the news release. “In lakritz, all types of neuronal cells formed at the right place and numbers, only the speed of differentiation was slightly off.”

The researchers found the brains of the lakritz zebrafish formed pretty normally, and they decided to review whether the fish could still perform tasks connected to vision. They reviewed 2 such behaviors: orientation towards prey and so-called optokinetic eye movements, which are normally used to stabilize an image of the outside world.

Optogenetic light switches

“Since lakritz cannot see, they normally will never perform these behaviors, but the brain circuits might still be there waiting to act,” Sherman said in the institute’s news release.

To test this, the team utilized optogenetics to fire the neurons of the brain that generally are active when necessary. This method allows researchers to introduce ‘light switches’ into the neurons of living brains. This way they can remotely control neuronal activity, provided they find ways to stimulate the neurons from the outside with light, a task made easy in zebrafish due to their small size and transparency.

“Strikingly, lakritz reacted to the artificial stimuli as if they had actually seen a prey object,” Sherman said in the news release. “This shows us that the brain circuits required for these actions develop and function properly even when there is no input from the eyes at all.”

When considered as a whole, research from the Baier department shows that brain development is hardwired to a greater extent than previously thought.

“Shachar’s work shows that a complex part of the vertebrate brain, with many dozens of cell types, can develop just fine without sensory inputs,” Baier explained in the news release. “This highlights the power of genetically programmed algorithms in building the brain. If this works in zebrafish, why not also in larger animals?”

Researchers noted future studies may determine how strongly the development of sensory systems across the animal kingdom depends on input from the outside; the eyes and visual brain areas are just one example. The more scientists know about these processes, the closer they will get to answering the philosophical question of “what’s nature and what’s nurture?” or, in other words, whether brain wiring is innate and how much of it depends on our biography. For now, at least in the zebrafish visual system, nature appears to be the winner.

Reference:

1. Sherman, S., Arnold-Ammer, I., Schneider, M.W. et al. Retina-derived signals control pace of neurogenesis in visual brain areas but not circuit assembly. Nat Commun 14, 6020 (2023). https://doi.org/10.1038/s41467-023-40749-1