How do zebrafish know how to swim in groups?
When we organize a party, invite the family for a meal or go on an organized trip, we are motivated by the most basic element of social behavior: the desire to socialize with other human beings. Although the urge to spend time with our own kind is controlled to one degree or another by our genes, in humans it is difficult to know where the contribution of the genes ends and where the environmental influence begins. Weizmann Institute of Science scientists, in collaboration with researchers from Portugal, set out to examine these questions in a model animal, which, like humans, is also characterized by social behavior - zebrafish. In a new study recently published Researchers have uncovered a mechanism that wires the developing brain of zebrafish in a way that allows them to swim in groups as adults.
Zebrafish are an excellent model animal for studying the genetic basis of social behavior, as they do not receive any nurturing from their parents. "There are species of fish that invest in their offspring, but not zebra fish," says Prof. Gil Lebkowitz from the departments of molecular cell biology and molecular neurobiology, who headed the research team together with Prof. Rui Oliveira from the Gulbenkian Institute of Science in Portugal. "The female zebrafish lays several hundred eggs that are fertilized with the male's sperm after spawning. Besides a lunch box - a yolk sack attached to the egg - her message to her children is 'you'll manage on your own.'"
When the young fish finish the larval stage, at the age of about four weeks, and reach a length of one centimeter, they begin to mate with other fish. While they don't swim in beautifully organized schools like the moonfish in the Disney/Pixar animated film, Finding Nemo, they do show a distinct tendency to swim in groups. Similar to humans, they also have good reasons to seek company - swimming in a group gives them advantages in searching for food, overcoming currents in the water, avoiding predators and finding mating partners. But in order to behave in a group, zebrafish must be able to decipher visual and social stimuli: for example, know how to distinguish between "friends" and "enemies" - that is, identify members of their own species and make sure that it is not a different species, or God forbid, predators.
To find out how the neural wiring that enables social behavior is formed, postdoctoral researcher Dr. Ana Rita Nunes and research student Michael (Mikey) Glicksberg created a system designed to test the effect of the hormone oxytocin, known to increase social interactions, on the developing brain of zebrafish. They created transgenic stingrays whose nerve cells that produce oxytocin have a bacterial gene encoding Lethal sensitivity to antibiotics By adding antibiotics to the water, they were able to kill these nerve cells at various stages of the fry's development and track their behavior as adults.
The researchers discovered that without oxytocin in the early stages of development - more precisely, in the first two weeks of their lives - the stingrays developed into adult fish with reduced social skills, that is, those that do not swim in a school. Although the oxytocin-producing neurons did regrow later in development, it was already too late. In other words, for adult fish to be able to swim in groups, oxytocin must wire the brain in a certain way during a critical time window for its development.
Later, the scientists revealed the mechanisms by which oxytocin wires the developing brain. They found that the neurons that produce oxytocin were essential for the formation of another type of neurons - the producers of the neurotransmitter dopamine. As a result, in the brains of zebrafish that were not exposed to oxytocin in the first two weeks of life, two different areas of the brain were characterized by a low amount of both dopamine producers and connections to these neurons.
One of these areas is responsible for processing visual stimuli that are apparently essential for identifying swimming partners. In mammalian brains, including humans, a parallel area is responsible for processing visual information in social situations. For example, this area controls the eye movements that scan the face of the person in front of us to decipher an expression. In people with autism, this scanning pattern is often absent - evidence that their brains respond differently to socially meaningful visual information. The second area where dopamine was lacking corresponds to an important neural reward center in humans, involved in positive conditioning in social contexts.
Moreover, the lack of oxytocin in the early developmental stage also disrupted the "neural network for making social decisions" - a group of brain areas that work together to process social information. In fish whose brains developed without oxytocin, the timing patterns of neural activity between these regions were completely different from the patterns in normal fish.
"Our research shows that oxytocin is much more than the 'love hormone', the name that stuck to it - it plays a role in building neural systems that it uses later, including those involved in processing sensory information, cognitive processes, learning and reward," says Glicksberg. "Oxytocin organizes the brain in a way that is essential for handling social situations," Nunes concludes.
The mechanisms that were discovered in the research form the basis for new research directions of the influence of genetic programs on social behavior in humans, and in particular, the changes that oxytocin generates in the fetal brain. Understanding these mechanisms may advance the study of the molecular causes of various neurodevelopmental syndromes, including the autistic spectrum syndromes.
Dr. Susana Varla and Dr. Magda Teles from the Gulbakian Institute of Science participated in the study; Dr. Einat Wirzer and Dr. Jeanne Balchman from the Departments of Molecular Cell Biology and Molecular Neurobiology of the Weizmann Institute of Science; and Dr. Giovanni Petri from the Institute for Scientific Cooperation - ISI Foundation & ISI Global Science Foundation - in Turin, Italy.
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