Through the fish brain at the click of a mouse

A complex network of nerve cells (neurons) enables zebrafish to perceive their environment, find food or conspecifics for mating, or escape from enemies. All these cells have the same genetic information, but fulfil different functions in the brain. Specialisation for certain tasks is made possible by gene expression, i.e. the copying of genetic information into messenger RNAs and the translation into proteins. Gene expression determines the shape and connections of a neuron and determines its role in behaviour. Neurons with similar properties are grouped together to form nerve cell types, of which there are hundreds, if not thousands, in the fish brain. The situation is similar in the human brain.

In order to better understand how the brain works, scientists need to know which genes are expressed where. However, the nerve cell types underlying a particular behaviour are difficult to decipher. Maps that depict gene expression in the brain can help. However, the maps available to date still have many white areas.

„Until now, we only had fragmentary knowledge about gene expression in the zebrafish brain,

explains Inbal Shainer, postdoctoral researcher in Herwig Baier's department. „The data had low resolution and could not be combined with the latest cell type and brain structure maps of the fish. Our work now fills this gap.“

In order to fill the white areas in the existing maps with information, a team led by Inbal Shainer and Enrico Kuehn used a method that visualises the expression of individual genes under the microscope. As this analysis method is highly sensitive, it even makes differences in the gene expression of individual cells in the entire zebrafish brain visible at high resolution.

From the data obtained, the team created an expression map for each of the analysed genes and then combined hundreds of these maps into an atlas. This new gene expression atlas fits seamlessly into the previously developed 'Max Planck Zebrafish Brain Atlas' (mapzebrain), which contains information on brain structures, cell types and the connections between cells. By combining these features and gene expression, scientists can now gain a more complete picture of how the zebrafish brain processes information.

Using the new maps, the team investigated, for example, how environmental stimuli change the expression of the cfos gene in the zebrafish brain. This gene is expressed in active nerve cells and can therefore be used as an indicator of nerve cell activity. When the fish ingested food, the scientists observed an increase in cfos gene expression in an area of the brain that enables prey recognition and controls hunting movements. In addition, cfos gene expression increased in a group of cells connected to the lateral hypothalamus. This brain region presumably mediates the feeling of hunger or satiety.

„By integrating gene expression into the mapzebrain atlas, we have already gained some exciting initial insights. Further experiments will show whether the active cells we observed actually emit a stimulation signal,

says Enrico Kuehn, molecular biologist in Herwig Baier's department.

The Zebrafish Atlas is a free online tool and is constantly being expanded with new data sets by the research community. Scientists can view and analyse the maps online, download them to their devices or link the atlas to analysis programs.

The researchers in Herwig Baier's department are optimistic that the mapzebrain atlas will continue to grow. Additional genes and more detailed brain cell maps are to be added soon. Next, the team plans to incorporate information on neuronal circuits recently obtained using electron microscopy. „The combination of different data sets enables the zebrafish community to gain completely new insights into the genetic basis of brain function. This will allow us to better understand how brains develop and how they function,

says Inbal Shainer.

Press release by "idw - Informationsdienst Wissenschaft" from 22 February 2023