Researchers analysed mice's D1 and D2 neurons to understand how they code and respond to appetitive and aversive stimuli. The study revealed that, contrary to what was initially thought, these neurons are not functionally opposed, but rather complementary, and even tend to work together, albeit differently. Knowing this dynamic is fundamental to understanding illnesses such as post-traumatic stress or depression.

The human brain contains billions of neurons that continuously receive information and stimuli from the outside. To make decisions, neurons assess at every moment whether the stimulus is positive or negative. If it is positive, there is a tendency to approach, while if it is negative, an aversion reaction arises, which helps to ensure survival. The nucleus accumbens (NAc) of the brain plays a central role in the process of evaluating and coding stimuli, but how the D1 and D2 neuronal populations of the NAc encode appetitive or aversive stimuli is still not fully understood.

To deepen knowledge in this area, a team of researchers coordinated by Ana João Rodrigues and Carina Soares-Cunha (ICVS, U.Minho), with the support of the BIAL Foundation, studied the D1 and D2 neurons of the NAc to understand how they distinguish between stimuli and influence learning. By tracking hundreds of neurons in mice exposed to appetitive and aversive stimuli in real-time, the researchers demonstrated for the first time that D1 and D2 responded together to both stimuli.

In the article Dynamic representation of appetitive and aversive stimuli in nucleus accumbens shell D1- and D2-medium spiny neurons, published in the scientific journal Nature Communications, the researchers reveal that using advanced imaging in mice, they were able to observe that during associative learning, i.e. when a stimulus is associated with a reward or punishment, both types of neurons are activated and work together, but they do so differently. When associations change, such as when a negative stimulus no longer has an unpleasant consequence, the D2 neurons are essential for extinguishing that aversive association.

“Since difficulties in modifying negative associations are linked to anxiety and post-traumatic stress, better understanding the function of D2 neurons could help develop new treatments”, explains Carina Soares-Cunha. “The same external stimulus can provoke different reactions depending on the individual's context and memories. For example, the sound of fireworks can evoke celebrations and joy. Still, for a former combatant, it can trigger an anxiety crisis, bringing back memories of war, even if he is in a safe environment”, she exemplifies.

This study demonstrates the brain's ability to constantly reclassify external stimuli based on previous experiences and adapt to new situations while simultaneously proving the complexity of the neuronal circuits involved in this type of memory.

The work was developed in partnership with Rui Costa and Gabriela Martins from Columbia University and the Allen Institute (USA). In addition to the BIAL Foundation, the research was co-funded by the European Research Council, the la Caixa Foundation, and the Foundation for Science and Technology.

Learn more about the “175/20 - The role of nucleus accumbens in the perception of natural rewards” here.