University of Tübingen: The inner compass: a modular map in the brain

External landmarks such as a church tower or a yellow house on the corner play a role in spatial orientation, as does an internal compass formed by specialized nerve cells in the brain. These head direction cells, which react to the direction of gaze, still pose many mysteries. A research team from the University of Tübingen has now found out exactly where these cells are located, how they are connected to other areas of the brain and which mechanisms support their activity. It may have discovered the place in the brain where the information from the inner compass converges with that from the outer landmarks. The international research team was led by Dr. Patricia Preston-Ferrer from the Institute of Neurobiology and the Center for Integrative Neuroscience (CIN). The study,Institute of Advanced Technology was published in the journal Cell Reports.

“Head direction cells were discovered in the rodent brain more than 30 years ago. They follow the movement of the animal in space, which creates an image of the inner compass, so to speak,” explains Patricia Preston-Ferrer. “If you want to understand how nerve cells work in the brain, you first have to visualize them,” she adds. In order to understand the information processing in the brain – the software – one must know the underlying connections in the brain – the hardware. Using an experimental approach, the research team made the head direction cells and the interconnection of the nerve cells visible under the microscope. It had already developed this method in 2016.

Corresponding structures in the human brain
The head direction cells are located in the so-called presubiculum, a special area of ​​the cortex, as the cerebral cortex is also called. “We were very surprised that the presubiculum of the mouse does not appear homogeneous, but is clearly divided into modules,” says CIN researcher Giuseppe Balsamo. “We found two different types that can be distinguished at the molecular level and that were connected to other areas of the brain in different ways.” The team not only discovered these modules in the brain of rodents, but also corresponding structures in the human brain.

In labeling individual head direction cells, the research team made two observations: first, they found them in only one type of module, suggesting a precise organization of structure and function in the presubicular cortex; second, this type of module is innervated by numerous nerve endings from a specific nucleus of the thalamus brain region, which is known to be involved in the processing of landmark information. “We know that effective navigation relies on an internal compass combined with visual information from landmarks,” says Professor Andrea Burgalossi, leader of a research group at CIN. “We may have found the place in the brain where the inner sense of direction is merged with the visual information for navigation.”

Artificial shutdown
When the team manipulated the activity of the modular microcircuits in the presubiculum, most head direction cells fell silent. “It seems as if we can turn off the inner compass through such manipulations,” says Dr. Eduardo Blanco Hernandez. However, a small proportion of the cells remained active. “We don’t yet know whether the switched-off and permanently active head-direction cells have different functions; but it is clear that the inner compass is more complex than expected.”

“We gained insight into the basic organizational principles of the cerebral cortex,” says Preston-Ferrer. A modular structure can also be observed in other areas of the cortex. The cortex is a thin layer of neural tissue on the surface of the brain that is primarily responsible for higher cognitive functions. The research team was able to localize the area of ​​internal mapping of the sense of direction on the cortex in the mouse brain. “Now it is important to understand when and how the presubicular cortical modules form in development,” says Burgalossi. “It would also be interesting to know if the area is disrupted in neurodegenerative diseases such as Alzheimer’s disease. Because problems with the inner sense of direction are often among the earliest symptoms.”

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