Summary: The brain constantly evaluates whether stimuli are positive or negative, prompting approach or avoidance behaviors that are essential for survival. A new study reveals that two neuron types in the nucleus accumbens—D1 and D2 neurons—respond together to both rewarding and aversive stimuli, but in distinct ways.
Using real-time imaging in mice, researchers found that D2 neurons are especially important for updating learned associations, such as recognizing when a threat is no longer dangerous. These insights could help explain why people with anxiety or PTSD struggle to let go of negative memories and may lead to targeted treatments.
Key Facts:
- D1 and D2 Neurons: Both neuron types respond to rewards and threats but have different roles in learning.
- D2’s Role in Extinction: D2 neurons help extinguish negative associations when a stimulus is no longer aversive.
- Mental Health Implications: Understanding D2 function may inform new therapies for anxiety and PTSD.
Source: BIAL Foundation
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).
Funding: 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.
About this neuroscience research news
Author: Sandra Pinto
Source: BIAL Foundation
Contact: Sandra Pinto – BIAL Foundation
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Dynamic representation of appetitive and aversive stimuli in nucleus accumbens shell D1- and D2-medium spiny neurons” by Carina Soares-Cunha et al. Nature Communications
Abstract
Dynamic representation of appetitive and aversive stimuli in nucleus accumbens shell D1- and D2-medium spiny neurons
The nucleus accumbens (NAc) is a key brain region for motivated behaviors, yet how distinct neuronal populations encode appetitive or aversive stimuli remains undetermined.
Using microendoscopic calcium imaging in mice, we tracked NAc shell D1- or D2-medium spiny neurons’ (MSNs) activity during exposure to stimuli of opposing valence and associative learning.
Despite drift in individual neurons’ coding, both D1- and D2-population activity was sufficient to discriminate opposing valence unconditioned stimuli, but not predictive cues.
Notably, D1- and D2-MSNs were similarly co-recruited during appetitive and aversive conditioning, supporting a concurrent role in associative learning.
Conversely, when contingencies changed, there was an asymmetric response in the NAc, with more pronounced changes in the activity of D2-MSNs. Optogenetic manipulation of D2-MSNs provided causal evidence of the necessity of this population in the extinction of aversive associations.
Our results reveal how NAc shell neurons encode valence, Pavlovian associations and their extinction, and unveil mechanisms underlying motivated behaviors.
