The zebrafish offers new insights into the formation of neural networks in the human brain and pathologies such as bipolar disorder and schizophrenia
The zebrafish, a distant cousin of the common carp found in Quebec, is a small fish about 5 cm long, native to South Asia. It doesn’t use its brain to plan the week’s meals or its family’s annual vacation, to balance its personal life and professional obligations, to interpret a piece of music on the piano or to solve complex problems requiring elaborate abstract thought. And yet, the brain of this humble fish could reveal things about how our own brains work. Scientists from Laval University’s Faculty of Science and Engineering and the CERVO research center have demonstrated this in a series of experiments, the results of which have just been published in the journal Science Advances.
At first glance, the zebrafish brain pales in comparison to the human brain: the former has between 1 and 2 million neurons, while the latter has 86 billion. But, points out Professor Paul De Koninck, a specialist in molecular neuroscience and co-responsible for the study, "our understanding of the brain has been built up through studies of various animal species, from the tiny C. elegans worm to non-human primates. Although there are major differences between the brains of fish and humans, certain features, such as neuron architecture, synapse structure and the neurotransmitter system, have been conserved over the course of evolution."
These elements are not the only common denominators between the brains of different species, adds the study’s other co-leader, Professor Patrick Desrosiers , a specialist in theoretical physics and neural networks. "The way neurons are connected to each other also follows certain rules that transcend the species barrier. There are two forms of connectivity between neurons," he points out. The first, anatomical in nature, depends on the physical connections between neurons. The second, known as functional, is measured by the coordinated activity of neurons or brain regions. Neurons or brain regions may be relatively far apart physically, but functionally very close together."
In humans, functional connectivity is measured using magnetic resonance imaging or electroencephalography. "It is established by observing which areas of the brain are activated simultaneously, either spontaneously or when performing a task. However, the information we can obtain from these approaches has poor spatial and temporal resolution. They do not allow us to understand what happens at the cellular level during the formation of neuronal networks", explains Professor De Koninck.
To fill this gap, doctoral student Antoine Légaré used optogenetic and neurophotonic tools to measure the activity of over 54,000 distinct neurons in 65 brain regions of zebrafish aged 5 to 7 days. That’s about half of all the neurons that make up the brain of this fish at this stage. These data enabled him to map functional connectivity between neurons and between brain regions. He then cross-referenced this data with an atlas in which the anatomical connections of some 4,300 neurons in the zebrafish brain are collated.
what Antoine’s remarkable work has brought to light is that the basic principles of neural network organization seem to be similar in zebrafish and humans," sums up Patrick Desrosiers. I’m not saying that the zebrafish brain is equal to the human brain, but so far we haven’t discovered any whole-brain features of neural networks that are exclusive to humans."
"Even though the zebrafish brain is small, has relatively few neurons and its brain regions are organized differently, the way information flows between its brain regions shows great similarities to what is observed in humans. This makes it a very interesting model for studying the functional connectivity of the human brain", says Prof. De Koninck.
This study is fundamental in nature, but could have very concrete repercussions, continues the researcher. "Certain neurological or psychiatric disorders could result from a disturbance in the pruning of neuronal connections. For example, too much or too little pruning during adolescence could be implicated in diseases such as schizophrenia or bipolar disorder. Moreover, the zebrafish offers a very practical and inexpensive model for studying the effect of drugs or certain environmental factors on the development of neuronal networks. In fact, we want to use it to study how microbiota can influence this development."
The signatories of the study published in Science Advances are Antoine Légaré, Mado Lemieux, Vincent Boily, Sandrine Poulin, Arthur Légaré, Patrick Desrosiers and Paul De Koninck.
