Modelling the emergence of whisker barrels

Abstract

Brain development relies on an interplay between genetic specification and self-organization. Striking examples of this relationship can be found in the somatosensory brainstem, thalamus, and cortex of rats and mice, where the arrangement of the facial whiskers is preserved in the arrangement of cell aggregates to form precise somatotopic maps. We show in simulation how realistic whisker maps can self-organize, by assuming that information is exchanged between adjacent cells only, under the guidance of gene expression gradients. The resulting model provides a simple account of how patterns of gene expression can constrain spontaneous pattern formation to faithfully reproduce functional maps in subsequent brain structures.

eLife digest

How does the brain wire itself up? One possibility is that a precise genetic blueprint tells every brain cell explicitly how it should be connected to other cells. Another option is that complex patterns emerge from relatively simple interactions between growing cells, which are more loosely controlled by genetic instruction.

The barrel cortex in the brains of rats and mice features one of the most distinctive wiring patterns. There, cylindrical clusters of cells – or barrels – are arranged in a pattern that closely matches the arrangement of the whiskers on the face. Neurons in a barrel become active when the corresponding whisker is stimulated. This precise mapping between individual whiskers and their brain counterparts makes the whisker-barrel system ideal for studying brain wiring.

Guidance fields are a way the brain can create cell networks with wiring patterns like the barrels. In this case, genetic instructions help to create gradients of proteins across the brain. These help the axons that connect neurons together to grow in the right direction, by navigating towards regions of higher or lower concentrations. A large number of guidance fields could map out a set of centre-point locations for axons to grow towards, ensuring the correct barrel arrangement. However, there are too few known guidance fields to explain how the barrel cortex could form by this kind of genetic instruction alone.

Here, James et al. tried to find a mechanism that could create the structure of the barrel cortex, relying only on two simple guidance fields. Indeed, two guidance fields should be enough to form a coordinate system on the surface of the cortex. In particular, it was examined whether the cortical barrel map could reliably self-organize without a full genetic blueprint pre-specifying the barrel centre-points in the cortex.

To do so, James et al. leveraged a mathematical model to create computer simulations; these showed that only two guidance fields are required to reproduce the map. However, this was only the case if axons related to different whiskers competed strongly for space while making connections, causing them to concentrate into whisker-specific clusters. The simulations also revealed that the target tissue does not need to specify centre-points if, instead, the origin tissue directs how strongly the axons should respond to the guidance fields. So this model describes a simple way that specific structures can be copied across the central nervous system.

Understanding the way the barrel cortex is set up could help to grasp how healthy brains develop, how brain development differs in certain neurodevelopmental disorders, and how brain wiring reorganizes itself in different contexts, for example after a stroke. Computational models also have the potential to reduce the amount of animal experimentation required to understand how brains are wired, and to cast light on how brain wiring is shaped by evolution.