Reprogramming Brain Cells Enables Flexible Decision-Making

Summary: Study identifies neurons in command of guiding adaptive behaviors.

Source: University of Zurich

Humans, like other animals, have the ability to constantly adapt to new situations. Researchers at the Brain Research Institute of the University of Zurich have utilized a mouse model to reveal which neurons in the brain are in command in guiding adaptive behavior. Their new study contributes to our understanding of decision-making processes in healthy and infirm people.

Greetings without handshakes, mandatory masks in trains, sneezing into elbow crooks – the COVID-19 pandemic dramatically illustrates how important it can be for humans to shed habitual behaviors and to learn new ones. Animals, too, must be capable of rapidly adapting to changes in environmental conditions.

“The plasticity of the brain forms the foundation of this ability,” says Fritjof Helmchen, the co-director of the Brain Research Institute at the University of Zurich, who also heads the Neuroscience Center Zurich. “But the biological processes that enable this amazing feat are still poorly understood.” Helmchen’s team has now successfully taken a first step towards illuminating these processes.

Their study, just published in the scientific journal Nature, demonstrates that the orbitofrontal cortex, a region of the cerebral cortex that sits behind the eyes, is capable of reprogramming neurons located in sensory areas.

Observing brain cells in the act of relearning

In their experiments with mice, the researchers simulated a relearning process under controlled conditions and investigated what happens in the brain at the level of individual neurons during that process. The researchers first trained the animals to lick every time they touched a strip of coarse-grit sandpaper with their whiskers and rewarded the response with a drink of sucrose water.

However, the mice were not allowed to lick when they brushed their whiskers against fine-grain sandpaper; if they did, they were punished with a mild irritating noise. Once the mice understood how to perform their task, the tables were then turned. The reward was now delivered after whisking against fine-grain and not coarse-grit sandpaper. The mice quickly learned this new, opposite behavior pattern after little practice.

A higher authority remaps cells

During the training, the neuroscientists employed molecular biological and imaging techniques to analyze the function of individual neurons in the brain cortices involved.

Their analysis revealed that a group of brain cells in the orbitofrontal cortex is particularly active during the relearning process. These cells have long axons that extend into the sensory area in mice that processes tactile stimuli. The cells in this area initially followed the old activity pattern, but some of them then adapted to the new situation. When specific neurons in the orbitofrontal cortex were deliberately inactivated, relearning was impaired and the neurons in the sensory area no longer exhibited modification in their activity.

“We were thus able to demonstrate that a direct connection from the orbitofrontal cortex to sensory areas of the brain exists and that some neurons get remapped there,” explains Helmchen.

“The plasticity of those cells and the instructions they receive from the higher-order orbitofrontal cortex appear to be crucial to behavioral flexibility and our ability to adapt to new situations.”

This shows the location of the orbitofrontal cortex
The orbitofrontal cortex. Image is credited to UZH.

“It has long been known that the orbitofrontal cortex is involved in decision-making processes”. It is in charge, to a certain degree, of enabling us to react appropriately and successfully to exogenous circumstances.

“But the neural circuits underlying this function were unknown until now,” says Abhishek Banerjee, lead author of the study, now an Associate Professor at Newcastle University, UK.

“This mode of communication and control across distant areas of the brain is truly remarkable.”

Understanding disorders better

The researchers believe that the fundamental processes they observed in mice take place in a similar way in the human brain as well. “This deepened knowledge about complex brain processes involved in decision making is important,” explains Helmchen.

“Our research findings may contribute to a better understanding of brain disorders in which the flexibility in decision making is impaired, as it is, for example in various forms of autism and schizophrenia.” Clearly, he says, having difficulties or being unable to adapt one’s behavior poses a severe problem for affected people.

About this neuroscience research article

University of Zurich
Fritjof Helmchen – University of Zurich
Image Source:
The image is credited to UZH.

Original Research: Closed access
“Value-guided remapping of sensory cortex by lateral orbitofrontal cortex” by Abhishek Banerjee, Giuseppe Parente, Jasper Teutsch, Christopher Lewis, Fabian F. Voigt & Fritjof Helmchen. Nature.


Value-guided remapping of sensory cortex by lateral orbitofrontal cortex

Adaptive behaviour crucially depends on flexible decision-making, which in mammals relies on the frontal cortex, specifically the orbitofrontal cortex (OFC). How OFC encodes decision variables and instructs sensory areas to guide adaptive behaviour are key open questions. Here we developed a reversal learning task for head-fixed mice, monitored the activity of neurons of the lateral OFC using two-photon calcium imaging and investigated how OFC dynamically interacts with primary somatosensory cortex (S1). Mice learned to discriminate ‘go’ from ‘no-go’ tactile stimuli and adapt their behaviour upon reversal of stimulus–reward contingency (‘rule switch’). Imaging individual neurons longitudinally across all behavioural phases revealed a distinct engagement of S1 and lateral OFC, with S1 neural activity reflecting initial task learning, whereas lateral OFC neurons responded saliently and transiently to the rule switch. We identified direct long-range projections from lateral OFC to S1 that can feed this activity back to S1 as value prediction error. This top-down signal updated sensory representations in S1 by functionally remapping responses in a subpopulation of neurons that was sensitive to reward history. Functional remapping crucially depended on top-down feedback as chemogenetic silencing of lateral OFC neurons disrupted reversal learning, as well as plasticity in S1. The dynamic interaction of lateral OFC with sensory cortex thus implements computations critical for value prediction that are history dependent and error based, providing plasticity essential for flexible decision-making.

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