How does our brain switch between different behaviours? A current study has now provided the first answers to this key question in neuroscience. Using mice, the researchers investigated electrical activity in a certain area within the brain. Results were then analysed with the help of an adaptive computer algorithm. This artificial intelligence identified a type of typical fingerprint in the signals. Analysing this signal allowed researchers to predict which behaviour the animals would switch to next, two seconds before they actually made the change. The study was conducted at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), University Hospital Cologne, the Max Planck Institute for Metabolism Research and the University of Cologne’s CECAD Cluster of Excellence in Aging Research. The results have now been published under “The dynamic state of a prefrontal–hypothalamic–midbrain circuit commands behavioral transitions” in the journal Nature Neuroscience.

We do thousands of different things every day: we talk on the phone, we write emails, we eat, we do sport, we brush our teeth. How does our brain manage to switch between these different behaviours? This question is currently the subject of intense research in neuroscience. If this central function of our brain fails to work properly, it can lead to major neuropsychiatric disorders, such as binge eating, anorexia or obsessive-compulsive disorder.

A certain area within the brain plays an important role in making these transitions: the hypothalamus. Its role is akin to that of an air traffic controller. It acts as a hub where important information about the body comes together – whether we are hungry, how high our body temperature is, how fast our heart is beating. The rest of the brain keeps the hypothalamus informed about the external world. Based on this information, the hypothalamus regulates innate behaviours such as eating, exploring surroundings or interacting with others. But how does it do so?

To answer this question, a tandem of research groups led by Professor Dr Alexey Ponomarenko (Institute of Physiology and Pathophysiology at FAU) and Professor Dr Tatiana Korotkova at University Hospital Cologne and the MPI for Metabolism Research combined several cutting-edge techniques of neuroscience and mathematics. The researchers investigated the hypothalamus in mice, as this part of the brain is very similar in mice and humans. “We used AI to analsze the electrical activity in a certain region within the hypothalamus,” explained data scientist Mahsa Altafi, a doctoral candidate at FAU.

Initial findings revealed that the hypothalamus oscillates at a rhythm known as a beta oscillation. The nerve cells in the hypothalamus are particularly active twenty times a second, with activity levels falling again between these peaks. It is like an orchestra in which all the musicians concentrate on the conductor’s baton in order to play in unison. What is particularly interesting is that some cells do not become active on tact, but just before, in the offbeat. These cells play a certain melody. And the order of the notes they played influences which piece of music the orchestra plays next. “Reading the electrical signal allows us to predict which behavior the mouse will switch to two seconds later,” Altafi said.

But what happens if the offbeat melody is suppressed? Changwan Chen at the Max Planck Institute for Metabolism Research and University Hospital Cologne used light to manipulate the activity of the hypothalamic neurons. The effect was surprising: the mice remained stuck in their current behaviour until the light was switched off. For example, they interacted persistently with other mice even if these mice showed no interest. “It was striking how persistently a mouse with the inhibited transition state interacted with another mouse that was trying to avoid this prolonged communication,” Chen recalls.

The “offbeat melody” appears to put the hypothalamus in a transition state, thereby enabling the animals to switch to another behaviour. Which behaviour that is, however, does not depend solely on the hypothalamus. It turns out that the hypothalamus is instructed by the medial prefrontal cortex, a region responsible for cognitive control of behaviour. For example, it considers which option is best in a particular situation. Should I eat? Or should I rather interact with another mouse, or collect new experiences?

In order to communicate with the hypothalamus, the medial prefrontal cortex oscillates in tact with the rhythm set by the hypothalamus, following the beta oscillation like a conductor’s baton. “Signals from the prefrontal cortex help the hypothalamus to promote transitions between behaviours,” explained Korotkova, who is also Principal Investigator at the UoC’s CECAD Cluster of Excellence in Aging Research. “It is particularly fascinating that the hypothalamus starts a preparation to transition between behaviours around two seconds before it actually occurs. It is likely that the mice are not even consciously aware at this point that they are about to switch to a different behavior.”

“Our findings indicate the importance of beta oscillations in orchestrating the activity of the myriads of neurons that drive specific behaviours, and for smooth transitions between them,” said Ponomarenko. “These findings may guide the development of new medications and therapies for serious psychiatric brain disorders. I look forward to the day when patients with anorexia nervosa or obsessive-compulsive disorder can benefit from this.”

Media Contacts:
Professor Dr. Alexey Ponomarenko
Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
+49 9131 85 29302
alexey.ponomarenkofau.de

Professor Dr Tatiana Korotkova
University Hospital Cologne/University of Cologne / CECAD Cluster of Excellence in Aging Research
tatiana.korotkovauk-koeln.de

Publication:
https://www.nature.com/articles/s41593-024-01598-3